AntiBody&BeYond

 

 

Methods and Techniques For Life Scientists

p53 Antibody Review

 

 

 

Introduction

  • a recessive tumor suppressor gene located on chromosome 17p. PMID: 8126158

  • a 53 kD phosphoprotein and gene product of the p53 gene. PMID: 9225141

  • a tumor suppressor gene encoding a nuclear phosphoprotein that plays an important role in the control of normal cell proliferation. PMID: 10732866

  • a tumour suppressor gene, which is mutated in more than half of all tumours. PMID: 17593631

  • a transcription factor with sequence-specific DNA binding properties. PMID: 10725451

  • a key player in the cellular response to stress conditions. PMID: 12824537

  • a major regulator of cell cycle progression and apoptosis. PMID: 11668189

  • The most frequently mutated tumor suppressor gene found in human cancer. PMID: 17301441

  • a transcription factor that plays a key role in the prevention of cancer development. Mutation of the p53 gene is the most common genetic alteration in human cancer, affecting more than 50% of human tumors. PMID: 17419939

  • play a role in malignant transformation. PMID: 1607637

  • frequently mutated in highly proliferating carcinomas. PMID: 14989491

  • essential for DNA damage-induced trophoblastic apoptosis. PMID: 17594519

  • a fundamental determinant of cancer susceptibility and other age-related pathologies. PMID: 17310982

  • plays a central role in the DNA damage response. PMID: 17031865

  • p53 regulates cell growth and abnormal p53 immunophenotypic expression is associated with an unfavorable prognosis for patients with some types of carcinoma. PMID: 8625155

  • a common target in carcinogenesis, reported to be altered and functionally inactive in 70% of human cancers. PMID: 15875732

  • a vital anticancer gene, controls the transcription and translation of a series of genes, and implement the cell cycle arrest and cell apoptosis by regulating their complicated signal pathways. PMID: 17512110

  • The product of mutated p53 gene is a protein with abnormal conformation, impaired DNA binding, and a prolonged half life, the latter of which results in immunohistochemically detectable levels within nuclei of malignant cells. PMID: 12044054

  • a tumour suppressor gene, is the most commonly mutated gene human cancer. PMID: 11820604

  • mutated p53 is one of the most frequent gene abnormalities in human cancer. PMID: 11368097, PMID: 11193185

  • The p53 gene is one of a family of tumor suppressor genes that have been implicated in the genesis of a wide variety of malignant neoplasms including Bowen's disease. PMID: 11244221

  • one of tumor suppressor genes that play a major role in signal transduction following many kinds of stresses, including ionizing radiation. PMID: 9683807

  • The p53 gene, which is located on human chromosome 17, encodes for a nuclear phosphoprotein and is thought to regulate cell growth and proliferation. PMID: 8958308

  • p53 mutations are known to occur frequently in human cancers where they are considered to be an important event in the stepwise progression towards malignant transformation. PMID: 8714263

  • The mutation of the p53 gene is a common phenomenon in numerous human tumors, leading to the accumulation of nonfunctioning p53 protein in the cell nucleus. PMID: 7579801

  • Stabilization of the mutant p53 protein allows immunohistochemical analyses (IHC) to be routinely used to demonstrate the mutant p53 protein in tissue samples, whereas normal p53 protein is undetectable. PMID: 7610836

  • The wild-type P53 protein, a product of the P53 gene, is a normal growth controlling protein. Mutation of the P53 gene generates a mutant P53 protein which promotes tumor formation through loss of growth suppression. PMID: 8223054

  • p53 gene is a transcription factor essential for the prevention of cancer formation. The p53 pathway is ubiquitously lost in human cancer either by p53 gene mutation (60% of cancers) or by lost of cell signalling upstream and downstream of p53 in the remaining cancers expressing WTp53 gene. PMID: 17637683

  • The p53 tumor suppressor gene, discovered some 30 years ago, has a key role in preventing cancer development. PMID: 17481900

  • The p53 family comprises the tumor suppressor p53 and the structural homologs p63 and p73. PMID: 17045206

  • The p53 gene is located on human chromosome 17p13.1 and comprises of 11 exons. PMID: 17041552

Normal Expression

  • Recently, p53 expression has been demonstrated in normal murine tissues, including whole eye. We found strong cytoplasmic p53 expression in the corneal epithelium of various vertebrate species by immunohistochemistry and by Western analysis. High levels of cytoplasmic p53 protein were normally found in normal corneal epithelium of various vertebrate species. Hence, these data may indicate that p53 may have a new evolutionary significant function in the eye. PMID: 16376331

  • p53 is expressed in both peripheral and central human corneal endothelium, although it is more highly expressed in the central endothelium. Similarly, TAp63 is more highly expressed in central rather than in peripheral endothelium. PMID: 15889017

  • High levels of p53 protein are found in various normal murine ocular tissues, especially the corneal and conjunctival structures and the lens epithelium. Each of these tissues demonstrate unique patterns of staining. PMID: 12036973

  • The wild type p53 protein has a short half-life and cannot be detected by immunohistochemistry on tissue sections. Mutated p53, on the other hand, has a prolonged half-life and becomes detectable by this method, so that its detection by immunohistochemistry in solid tumors is almost synonymous with mutation. PMID: 8057671

  • association of p53 with the plasma membrane is a normal, rather than a transformation-related phenomenon, and is temporally linked to the period of mitosis. PMID: 3006339

  • Detection of p53 immunoreactivity is uncommon in normal cells, but is frequently seen in neoplasia. PMID: 8038426

  • Immunostaining of wild type p53 is demonstrable not only in its nuclear form using antibody PAb240 but also in it common cytoplasmic-perinuclear localisation in normal tissues using the PAb248 monoclonal antibody. This opens up new possibilities for its study in both physiological and pathological conditions. PMID: 8089212

  • p53 protein was confined to the basal cell layer in normal oral mucosa and in the hyperplastic group. In the dysplastic group, it was expressed in the basal and suprabasal layer, whereas in invasive carcinoma, it was detected in central and peripheral regions. PMID: 17321451

  • an accumulation of wild-type p53 protein occurs in gastric cancer cells and represents a stress-response mechanism that lowers metastatic potential. PMID: 10868700

  • weak p53- and p21-nuclear reactivities were detectable in primary spermatocytes within normal seminiferous tubules. PMID: 10803982

  • Normally, p53 protein degrades rapidly and is not detected by immunohistochemical procedure, but mutant p53 and wild-type p53 stabilized by certain viral oncoproteins can accumulate to immunohistochemically demonstrable levels. PMID: 8751332

  • p53 protein was detected in the nuclei of a few trophoblastic cells, almost all belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in nearly all specimens investigated (first trimester 10/10, second trimester 5/5, third trimester 4/5). PMID: 7716122

  • Results showed p53 to be expressed in all oral lichen planus (OLP) lesions and normal tissues (matched normal controls). PMID: 17418619

  • DO7 antibody elicited strong nuclear staining in the mucosal cells of the small and large intestine, lymphoid cells, decidua, neurones such as Purkinje cells of the cerebellum, glandular epithelial cells and stromal cells of the prostate, cardiac myocytes and bronchial epithelial cells. Cytoplasmic staining was noted in Purkinje cells, glandular epithelium of prostate, exocrine pancreas and renal tubular epithelium. The 1801 antibody did not produce staining in any of these tissues. CONCLUSIONS: Our study demonstrates the presence of p53 in normal paraffin-embedded tissue with nuclear and/or cytoplasmic localization in some instances. In our view, DO7 appears to be better suited for such detection. PMID: 12493030

  • On the proestrus day, p53 protein was predominantly detected in the glandular epithelium. However, on the estrus day, p53 protein was detected both in the nuclei and in the cytoplasm of luminal epithelial cells, predominantly in the cytoplasm. PMID: 11891915

  • Positive immunoreaction for p53 was detected in six (20%) of the tissue samples in normal oral mucosa of heavy smokers. PMID: 11277333

Abnormal Expression

  • In ovarian cancer, the rate of p53 mutation has been shown to be very high and associated with poor prognosis. PMID: 17404014

  • p53 mutations are amongst the most prevalent alterations in human cancer. Overexpression of p53 is usually caused by mutation and is observed in a high percentage of squamous cell carcinomas of the head and neck (SCCHN). PMID: 9066697

  • P53-positive cells can be detected in washings using flow cytometry and were more commonly detected in association with aneuploid tumours. PMID: 8535675

  • Immunohistochemical detection of p53 protein is possible when the gene has been mutated, but not when the normal gene product alone is present. Our results indicate that this tumor suppressor gene may be involved in tumorigenesis, as its expression was detected in both borderline and malignant tumors while normal ovaries and benign ovarian tumors were unstained with the p53 antibody. PMID: 8206402

  • in stimulated lymphocytes p53 is progressively accumulated during the G1, S and G2-phases, while in non-stimulated conditions most cells are remaining in G0/G1 and express p53 to a lesser degree. PMID: 2140591

  • Mutation of the p53 tumour suppressor gene is thought to represent a significant step in the development of over half of all human cancers. PMID: 9189093

  • By immunohistochemistry, immunoreactive p53 was observed in the nuclei of carcinoma cells in 29 cases (59%). Relatively larger diameter tumors (more than 5cm), poorly differentiated tumors, tumors with distant lymph node metastasis, and DNA aneuploidy tumors were positive for p53 more frequently. PMID: 7915093

  • mitochondrial localization of endogenous p53 can be visualized by immunofluorescence of whole cells when stressed by hypoxic conditions. Suborganellar localization by limited trypsin digestion of isolated mitochondria from stressed cells suggests that a significant amount of mitochondrial p53 is located at the surface of the organelle. PMID: 11163756

  • The immunostaining in the chick epiblast was very clearly localized to the mitotic centrosomes and spindles, revealing a cytoplasmic location for p53 during mitosis and accounting for earlier reports of an association between p53, tubulin, and centrosomes. PMID: 10739659

  • p53 nuclear immunolabeling should be regarded as an independent biomarker of unfavourable Mixed mullerian tumor (MMT) behaviour. PMID: 9302556

  • Overall, a significant proportion of corticotroph adenomas studied expressed the p53 protein, which depending on the antibody used, was located either in the nucleus and/or the cytoplasm of tumorous corticotroph cells. Cytoplasmic accumulation of p53, as shown by our colocalization studies with HSP-70, may be due to p53/HSP-70 complex formation. PMID: 11081199

  • All 15 breast carcinomas (BCs) were comprised of distinct groups of cells which accumulated p53 in their nucleus and occasionally in their cytoplasm. PMID: 9137491

  • p53 is a frequently mutated gene in brain stem astrocytomas. It was found in 50 % of glioblastoma multiforme, 28.57% of grade III astrocytoma and 12.5% of grade II astrocytoma, while grade 1 astrocytomas failed to express p53 protein. p53 positivity was more in high grade lesions, decreasing significantly in lower grade lesions. PMID: 15659871

  • p53 protein overexpression was observed in 67% patients with pancreatic cancer, but not in patients with chronic pancreatitis. PMID: 15643503

  • p53 and c-fos are significantly overexpressed in thyroid cancer patients, indicating their role in the genetic mechanisms leading to thyroid tumorigenesis. This hypothesis is further supported by the observation that p53/c-fos coexpression was related with more advanced disease status. PMID: 12687275

  • p53 immunoreactivity is not limited to astrocytomas, but it can be observed in lesions that often are mistaken for glioma. No TP53 mutations accompany p53 expression in nonneoplastic lesions, and mdm2 may be responsible for persistence of p53 expression in these processes. PMID: 12383370

  • p53 immunoreactivity indicates gene mutation when the majority (> 75%) of neoplastic cells express p53, p53 mutations would seem uncommon in cervical carcinogenesis. Nonetheless, glandular malignancies, in particular poorly differentiated variants, may show a higher frequency of mutation. PMID: 12190289

  • In carcinomas, p53 was positive in 50% of CRC tissues and 60% of CAC tissues without statistical difference. Positive expression of p53 was found in most high-grade dysplasia but not in low-grade dysplasia (p < 0.01). PMID: 11865380

  • The mutation of the p53 gene is a common phenomenon in numerous human tumors including breast cancer. It leads to an accumulation of nonfunctioning p53 protein in the cell nuclei, which can be detected by immunohistochemical techniques. PMID: 11299837

  • Pancreatic cancer is characterized by a high expression of p53 and a low expression of bcl-2. PMID: 10732293

  • Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. PMID: 10492244

  • p53 mutations have been shown to occur at an earlier phase in the progression of chronic ulcerative colitis (CUC)-associated neoplasia when compared with sporadic colon carcinogenesis. PMID: 10435567

  • The expression of mutant p53 was observed in 74% of glioblastomas, wild-type p53 in 18% of glioblastomas. PMID: 10328545

  • p53 mutation is an early event in esophageal carcinogenesis occurring in most of the dysplasia (DYS) and carcinoma in situ (CIS) lesions, and cells with such mutations will progress to carcinoma, whereas the role of p53 mutations in basal cell hyperplasia (BCH) is less clear. PMID: 10223186

  • p53 protein was expressed only in the osteosarcomas, but that c-myc expression was detectable in both the epithelial and myoepithelial components. PMID: 10087490

  • accumulation of p53 protein is frequently encountered in both premalignant and malignant skin lesions of renal transplant recipients (RTRs), and that this may occur as an early step in transplant-associated skin carcinogenesis. PMID: 10037511

  • Our data demonstrate a statistically significant higher p53 expression rate in colonic carcinomas than in adenomas, and that adenomas with concurrent carcinomas are more frequently p53 positive than those without concurrent carcinoma, but this was not statistically significant. Also, p53 expression is more frequent and intense in adenomas with high-grade dysplasia (10/20, 50%) than in ordinary adenomas with low-grade dysplasia (8/29, 28%), which suggests a strong correlation between the degree of dysplasia in colonic neoplasia and p53 expression pattern. PMID: 9647033

  • In lung cancer patients, positive p53 staining was detected in 26/53 (49%) of the tumour specimens. In preneoplastic lesions p53 positive staining was found in 8 of 24 (33.3%) squamous metaplasia, 1 of 4 hyperplasia and 1 of 3 dysplasia lesions. In the same group of patients, 12 cases were found with positive p53 cells in normal bronchial mucosa. In patients with benign diseases, positive p53 staining was found in 1 of 4 cases with squamous metaplasia and in one normal mucosa. PMID: 9538190

  • It is also notable that a high proportion of the prostate cancers examined were immunopositive for p53. PMID: 9495727

  • The majority of Micropapillary serous carcinoma (MPSCs) demonstrated positive, but only moderately intense, p53 immunostaining in >50% of the cells, whereas serous borderline tumors (SBTs) showed very weak staining in a small number of cells. In contrast, the majority of serous carcinomas displayed diffuse, very intense staining and those that did not stain completely lacked any staining for p53. PMID: 9475193

  • the abnormal expression of cyclin A and p53 is associated with high-grade endometrial endometrioid carcinomas. PMID: 9421074

  • p53 overexpression is involved in the tumorigenesis of both components in the SpCC, and the spindle cell component shows a higher degree of proliferative activity than the carcinomatous component. PMID: 9211529

  • p53 protein expression occurs frequently in both malignant and dysplastic lesions of the oral cavity, suggesting that abnormally detectable p53 protein is present at the very early stages of development of oral squamous carcinoma. PMID: 9088674

  • p53 aberrations are very common in esophageal carcinomas. However, p53 gene mutation and p53 protein accumulation have a significant discordance, suggesting that p53 function may be inactivated by mechanisms other than mutation. PMID: 9028350

  • Seventy five percent of Kaposi's sarcoma (KS) lesions from transplanted patients presented both nuclear and cytoplasmic positive p53 immunostaining with DO-7 antibody, thus demonstrating a presumably functional inactivation. PMID: 9177500

  • The nuclear p53 immunoreaction rate is low in rhabdomyosarcoma (RMS), but p53 expression appears to correlate with poor prognosis. PMID: 9065719

  • Scattered nuclear and rare cytoplasmic positivity was present in one papilloma, which showed foci of increased mitotic activity (labeling index 2.5%). Six of six carcinomas were immunoreactive for p53, and three cases had labeling indexes of over 70%. All immunopositive choroid plexus tumors (7/7) exhibited nuclear staining. Punctate cytoplasmic positivity was identified in 5 of 7 cases. PMID: 12049110

  • the nuclei expressing p53 protein are larger than p53 negative nuclei. The level of immunohistochemical expression of p53 is low in primary skin melanoma, and it is not valuable as a general prognostic marker for this tumor. p53 expression is not associated with melanoma thickness, indicating that high p53 expression is not a late phenomenon in the progression of this tumor. PMID: 8897518

  • p53 overexpression was studied by immunohistochemistry in 96 consecutive colorectal cancer patients, subdividing positive specimens according to two staining patterns: cytoplasmic or nuclear. PMID: 9081357

  • the abnormal p53 expression has some relevance to the skin carcinogenesis of porokeratosis. PMID: 8675831

  • High levels of the p53 protein are immunohistochemically detectable in a majority of human nonmelanoma skin cancers and UVB-induced murine skin tumors. PMID: 8552621

  • In paraffin-embedded sections of human choriocarcinoma, staining was confined to the nuclei of malignant cells. The results suggest that p53 is overexpressed not only in malignant tumour cells but in certain trophoblast cell populations of the human placenta as well. PMID: 7650160

  • p53 overexpression occurs in dysplastic epithelium of precancerous gastric lesions. Its absence in chronic atrophic gastritis with intestinal metaplasia suggests it is a relatively late event in the gastric carcinogenic sequence. PMID: 8237942

  • The expression of the p53 gene, therefore, appears increased in the majority of pancreatic adenocarcinomas while this is not observed in chronic pancreatitis or normal pancreatic tissue. PMID: 8218996

  • expression of the p53 oncoprotein is a common finding in gastric cancer and occurs as a late event in the malignant transformation process. PMID: 8133401

  • The p53 over expression tended to be more frequent in colorectal carcinomas with high proliferative activity. PMID: 17592558

  • High nuclear p53 expression levels were associated with better outcome for overall survival (OS) (P = 0.0023) and disease-free survival (P = 0.0338) at 5-years. High cytoplasmic p53 expression levels were associated with better outcome for OS (P = 0.0002). PMID: 17220511

  • the expression of p53 in three out of four (75%) secondary GBM was confined to the nucleus and the p53 positive cells were randomly distributed throughout the tumor. The expression of p53 in four out of seven (57%) de novo GBM was cytoplasmic, diffusive, and confined to the perivascular region of the tumor. PMID: 17214319

  • Expression of p53 in virally infected tubular cells in renal transplant patients with polyomavirus nephropathy. PMID: 16733208

  • delayed degradation could be responsible for the cytoplasmic p53 accumulation. PMID: 16720642

  • The p53 gene is a tumor suppressor gene that is commonly mutated in skin cancer and sun-exposed skin, and this can be detected through immunohistochemical expression of the p53 protein. PMID: 16624969

  • P53 positive cells were located most commonly in the basal layer of the epidermis of both healthy skin and non-lesional psoriatic skin. In lesional psoriatic skin p53 positive cells were present in all layers of the epidermis. PMID: 16200332

  • p53 synovial tissue (ST) overexpression and association with joint damage is characteristic of rheumatoid arthritis (RA) rather than psoriatic arthritis (PsA), and that p53 ST expression might be a prognostic marker of joint damage in RA. PMID: 15647425

  • Overall 52% of supratentorial astrocytic tumors showed p53 immunopositivity with no correlation to the histological grade. Thus, 58.8% of diffuse astrocytomas (WHO Grade II), 53.8% of anaplastic astrocytomas (WHO Grade III) and 50% of glioblastomas (WHO Grade IV) were p53 protein positive. PMID: 15269478

  • We recently demonstrated that the p53 oncosuppressor associates to centrosomes in mitosis and this association is disrupted by treatments with microtubule-depolymerizing agents. Here, we show that ATM, an upstream activator of p53 after DNA damage, is essential for p53 centrosomal localization and is required for the activation of the postmitotic checkpoint after spindle disruption. PMID: 15181149

  • p53 gene is frequently mutated in HPV38-positive skin cancers and that HPV38 E6 does not promote p53 degradation. PMID: 15145527

  • p53 overexpression occurs mainly in neoplastic skin lesions, although it may also occur in squamous epithelium of inflammatory skin diseases such as PS, as well as in normal skin epithelium. PMID: 15143984

  • p53 overexpression, detected by immunohistochemistry, has frequently been reported in porokeratosis (PK), and p53 mutations are direct results of ultraviolet (UV) skin exposure and are directly involved in most common skin cancers. PMID: 12859744

  • Positive cytoplasmic p53 expression and nuclear p53 overexpression seem to relate to more aggressive features and unfavorable outcome in pharyngeal squamous cell carcinoma (PSCC). PMID: 12203805

  • Immunostaining for p53 was found in the neuronal nuclei of 18 meningiomas. PMID: 12172734

  • a cytoplasmic accumulation of wild-type p53 in human primary glioblastomas correlates with a certain intermediate filament protein expression, suggesting that it identifies a certain subset of tumors. PMID: 12084347

  • p53 protein overexpression was identified only in patients with SDS and in patients with refractory anemia; these groups exhibited comparable prevalences of 78% and 72%, respectively. None of the patients with acquired aplastic anemia, acquired cytopenias, or in the control group showed overexpression of p53 protein. PMID: 11900571

  • the first report of altered p53/TSP-1 function in association with clinically aggressive behavior in FH Wilms tumor. PMID: 11877681

  • p53 mutations are quite frequent in children with Burkitt's lymphoma and may play a role in lymphoma genesis or disease progression. PMID: 11723536

Expression Alteration

  • p53 is upregulated approximately 2-fold in the superior temporal gyrus of Alzheimer's patients compared to healthy elderly control subjects. PMID: 17399897

  • p53 alteration may have different roles in adenocarcinoma and in squamous cell carcinoma, such as a carcinogenic factor for both cellular types but progression only for adenocarcinoma. PMID: 16613347

  • p53 expression is increased in damaged neurons in models of ischemia and epilepsy. PMID: 11121541

  • p53 alterations in colon tumors: a comparison of SSCP/sequencing and immunohistochemistry. PMID: 15536342

  • A significant increase is shown in p53 and MDM2 expression in H. pylori-infected gastric mucosa as compared to normal gastric mucosa; but successful eradication of H. pylori dramatically reduced the p53 and MDM2 levels. PMID: 15946145

  • p53 was highly prevalent in the contiguous squamous mucosa when it is present in Barrett's esophagus (BE). After ablation, none of the cases lost p53 expression, and none of the negative cases turned out to be positive. PMID: 15932166

  • alterations in bcl-2 and p53 may be associated with the malignant transformation of endometriotic cysts. PMID: 12115382

  • p53 alterations are infrequent in CCSK and do not seem to be primary genetic events in the pathogenesis of clear cell sarcoma of the kidney (CCSK). PMID: 12065773

  • p53 gene alterations may have an important role to play in the aggressive biological behavior and poor prognosis of this tumor. PMID: 11414195

  • structural and/or functional alterations at p53 gene are commonly observed in breast tumors. PMID: 11024482

  • HPV and p53 protein alterations frequently coexist in the lesions of our study and suggest that p53 mutation may be an early genetic event in oral carcinogenesis. PMID: 9891518

  • p53 mutations are frequent in breast tumours associated with unfavorable prognosis, including high-grade or the comedo histotype. There is evidence that p53 gene alterations occur early in breast cancerogenesis, as mutations were detected not only in in situ carcinomas but also in atypical ductal hyperplasia. PMID: 9428925

  • p53 alterations are found in the preponderant majority of post-radiation locally recurrent prostatic carcinoma specimens. PMID: 8627854

  • p53 alterations occur at different frequencies in various subtypes of sarcoma and, although detected in metastatic lesions, are not associated more frequently with progression. PMID: 8821948

  • altered p53 protein (probably mutant) is overexpressed in conventional adenocarcinomas and may be involved in its tumorigenesis or progression. PMID: 8751332

  • alteration of the p53 gene is implicated in the development of cancers complicating ulcerative colitis, as it is in the development of sporadic colorectal cancers, and it appears to be involved at a relatively early stage. PMID: 8563884

  • genomic alterations of the p53 gene are quite common events associated with special types of breast carcinoma, particularly of the apocrine subtype, but the prognostic value is unlikely to be of clinical importance. PMID: 7562251

  • The results of the present immunohistochemical study of p53 accumulation in gastric carcinomas suggest that gene alterations of p53 are not rare in gastric carcinomas and may participate in the carcinogenesis of intestinal-type carcinomas of the stomach. PMID: 8116572

  • the cytoplasm contains a separate and distinct p53 pool that is the major source for p53 translocation to the mitochondria upon its stress-induced stabilization. Using various manipulations that enhance or diminish p53 ubiquitylation, our data provide evidence that Mdm2-mediated monoubiquitylation of p53 greatly promotes its mitochondrial translocation and thus its direct mitochondrial apoptosis. PMID: 17268548

  • p53 protein is present in synapses where its level and amount of phosphorylation are increased following exposure of the cells to the DNA-damaging agent etoposide. PMID: 12835511

Function

  • p53 mutation might induce enlargement of neoplastic cell nuclei by some molecular mechanism. PMID: 17587242

  • wild-type p53 can reduce the apparent gain-of-function hypermutable effects of a particular p53 gene mutation and thereby help maintain genomic stability. PMID: 17567629

  • endogenous p53 in SiHa cells has an antioxidant function and involves in the reinforcement of the antioxidant defense. PMID: 17567683

  • p53 protein plays a central role in mediating stress and DNA damage responses, leading to either growth arrest or apoptosis. PMID: 17567589

  • The tumor suppressor protein p53 regulates expression of several genes, which mediate cell cycle arrest, apoptosis, DNA repair and other cellular responses. PMID: 17555406

  • The higher the amount of p53 stained, the higher the rate of tumor cell proliferation. However, there was no statistically significant association between p53 protein overexpression and clinical status, including tumor volume, nodal status, and metastatic condition. PMID: 17539259

  • activation of p53 is an important factor in metal regulation of metallothionein (MT). PMID: 17477370  

  • p53 plays a functional role in oxidative stress-induced cell death and supports the possibility that elevated p53 could be involved in motor neuron death in ALS and the wobbler mouse. PMID: 17434459

  • p53 may play a role in determining gefitinib sensitivity by regulating Fas expression in non-small cell lung cancer (NSCLC). PMID: 17283151

  • p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. PMID: 16728594

  • evidence exists that p53 has an extranuclear role in the cytoplasm to induce apoptosis. Recently, p53 has been shown to directly activate the pro-apoptotic Bcl-2 protein Bax allowing for mitochondrial membrane permeabilization and apoptosis. PMID: 15020844

  • p53 may have a separate cytoplasmic role in directly regulating the Bax-dependent mitochondrial pathway to cell death. PMID: 14980216

  • wild-type p53 enhances macrophage differentiation, while various p53 mutant types exert different effects on this differentiation pathway. PMID: 14713961

  • p53 plays a major role in the progression of carcinoma of the small intestine, whereas the role of K-ras mutation is much less significant. PMID: 11836595

  • p53 overexpression plays a different role in tumor carcinogenesis and progression of these two types of gastric cancers. PMID: 11422805

Diagnostic & Therapeutic Value

  • alteration of p53 expression in patients with high risk of lung cancer was an early event: this abnormality increased with the severity of the lesions, without significant correlation with patient characteristics. PMID: 11836584

  • Overexpression of p53 in malignant gliomas during childhood is strongly associated with an adverse outcome, independently of clinical prognostic factors and histologic findings. PMID: 11832530

  • restoring p53 function alone is sufficient to cause regression of several different tumor types in mice and thus might represent a potent therapeutic strategy to treat certain human cancers. PMID: 17350571

  • Restoration of Wild-Type p53 Function in Human Tumors: Strategies for Efficient Cancer Therapy. PMID: 17419952

  • p53 protein stabilization and p53 mutation frequently occur in STS, and both suggest worse outcomes for patients so affected. However, increased p53 protein expression does not necessarily indicate p53 gene mutation. PMID: 17429838

  • p53 expression may be a useful tool in classifying and predicting the prognosis of gastrointestinal stromal tumors as it is well correlated with tumor size, mitotic index, cellularity, and diagnosis according to our study results. PMID: 17419248

  • p53 immunoreactivity is a prognostic factor for patients with adenocarcinoma of stomach or gastroesophageal junction treated with adjuvant chemotherapy. PMID: 16277093

  • screening for p53 and Ki-ras mutations can be a useful adjunct in surveillance of patients with long-standing ulcerative colitis. PMID: 11761024

  • Loss of wild-type p53 function may therefore contribute to the development of aneuploidy in head and neck cancer. PMID: 11029495

  • p53 expression has important clinical implications as an indicator of prognosis and response to chemotherapy or radiotherapy in different human tumor types. PMID: 9405493

  • Immunohistochemical determination of p53 protein and FCM DNA analysis can aid in making an accurate and specific diagnosis of serous effusions, but the principal limitation of these tests is their relatively low sensitivity. PMID: 9390131

  • p53 Immunostaining of serous fluids seems to be of value in identifying carcinoma cells, especially in those cases that show inconclusive or bland cytologic features. Combining p53 with CEA immunostains in clinically or cytologically suspicious cases may assist in recognition of carcinoma cells and in pursuing an appropriate therapeutic approach. PMID: 9850638

  • MIB-1 and p53 co-staining is very useful for differentiating pilocytic astrocytomas and astrocytomas from anaplastic astrocytomas and glioblastomas. PMID: 9839169

  • p53 immunocytochemistry using ERPDB in conjunction with conventional cytologic examination can help differentiate ductal cell carcinoma from chronic pancreatitis preoperatively. PMID: 8635089

  • Immunohistochemical studies for p53 were found to be useful for predicting chemosensitivity. PMID: 15901938

  • p53 immunohistochemical staining could be a useful histological marker to complement routine histology in cancer surveillance programs in ulcerative colitis patients. PMID: 12818291

  • p53 immunohistochemistry qualifies as a diagnostic technique suitable for clinical practice in a community hospital. Its detection may be particularly promising in clinical trials of new molecular therapies directed at the p53 tumor suppressor gene. PMID: 11900572

  • Biopsy p53 status significantly predicts recurrence after radical prostatectomy, but its low specificity and technical issues suggest that it will not be useful in the clinical setting. However, a patient with negative p53 on biopsy is likely to have a good prognosis on prolonged follow-up. PMID: 11849156

  • p53-overexpression in bronchial dysplastic areas may be a clinically useful marker for identifying patients proceeding to, at least, squamous cell carcinoma and, in addition, may facilitate the detection of occult tumours. PMID: 10759451

  • p53 Immunohistochemistry, using monoclonal antibody DO-7 combined with standard morphologic evaluation, may be useful in distinguishing benign reactive mesothelium from borderline or low grade ovarian carcinoma. PMID: 10667156

  • p53 abnormalities play an important role in UC-associated tumorigenesis in its relatively early phase. For the diagnosis of dysplasia and carcinoma in UC, p53 IHC seems to be useful. PMID: 10571818

  • p53 IHC positivity with a multilineage pattern may be a characteristic of MDS in older patients. PMID: 10487829

  • p53 immunohistochemistry facilitates the interpretation of Barrett's epithelium but need only be employed to confirm a suspected diagnosis of dysplasia and assist with the distinction between low- and high-grade dysplasia. PMID: 9643490

  • If monoclonal antibodies with an epitope in the N-terminal region of the p53 protein (DO-1, Pab1801, DO-7) are applied, p53 immunohistochemistry provides an independent prognostic marker in STS (primary soft-tissue sarcomas). PMID: 9341900

  • Generally, p53 mutations and p53 overexpression are more likely to represent a late event in the oncogenesis of soft-tissue tumors. PMID: 9177493

  • p53 immunoreactivity in astrogliosis is unusual but is to be expected in astrocytomas and can help to differentiate reactive from neoplastic astrocytic lesions. PMID: 8764745

  • p53 alterations are related to the standard prognostic markers of endometrial cancer, i.e. grading and staging. TGGE, an indirect screening procedure for p53 mutations, is used to detect the type of p53 alteration and may provide additional insight into the complex figure of p53 abnormalities in the development and progression of malignant endometrial lesions. PMID: 8646368

  • Use of a cDNA-based sequencing method to determine the status of the p53 gene in primary breast cancers yielded better prognostic information than IHC performed with the Pab 1801 monoclonal antibody. PMID: 8632491

  • immunohistochemistry is valuable for assessing p53 gene mutations in colorectal neoplasms, but further study is needed to elucidate the precise link between immunohistochemistry and molecular genetic alterations. PMID: 7931827

  • The up-regulated expressions of mutant p53 and ki-67 are involved in the carcinogenesis and progression of gastrointestinal adenoma and adenocarcinoma (GIA). They appear to be objective and effective markers to reflect the development of GIA. PMID: 16821616

  • Expression of p53 protein has a statistically significant impact on disease-free survival in adenocarcinoma of the uterine cervix treated with RT alone. PMID: 15337561

  • The assessment of p53 activity and cell proliferation rate in gastric carcinoma is of prognostic value especially if evaluated together with other clinical and histopathological characteristics. The examination of these markers is useful in detecting early gastric cancer, in selecting high-risk patients and in planning proper individual treatment. PMID: 15011884

  • Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of hepatocellular carcinoma (HCC) patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis. PMID: 12046070

  • downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival. PMID: 11923604

  • p53 expression in Wilms tumor detected by immunohistochemistry seems to be associated with advanced disease and relapse. PMID: 11745874

  • the prognostic value of p53 protein expression was independent from that of both the nodal status and ER status in breast cancer. PMID: 11668240

  • Our data seem to indicate an unfavorable prognostic role of higher nuclear p53 expression. However, we believe that our results need to be integrated with patients' clinical follow-up and with the study of the expression of these markers in benign melanocytic lesions to gain more accurate information about their prognostic significance. PMID: 11504374

  • Failure to demonstrate p53 protein accumulation does not ensure a favourable outcome for pituitary adenoma. Accordingly, pituitary carcinoma may occur in the absence of p53 accumulation. PMID: 11383946

  • p53 colocalization with LGD at index LGD diagnosis is a risk factor for progression of LGD. This can potentially be used to risk stratify BE LGD patients in terms of surveillance intervals or enrollment into secondary prevention studies. PMID: 11374668

  • Immunohistochemical assessment of Ki67 and p53 expression assists the diagnosis and grading of ulcerative colitis-related dysplasia. PMID: 10931232

  • both p53 expression and PCNA are markers of poor differentiation in breast cancer. PMID: 10927863

  • the expression of mutant p53 proteins in small-cell lung cancer (SCLC) may be an important factor predicting poor prognosis. PMID: 10880844

  • An immunohistochemical analysis of p53 and the Ki-67 labeling percentage using biopsied specimens was thus found to effectively predict the efficacy of neoadjuvant therapies in patients with esophageal cancer. PMID: 10791203

  • lymph node expression of Mp53P is associated with increased mortality in Duke's B CRC. PMID: 10682269

  • Determination of p53 overexpression and reduced or absent expression of ER and PgR may help predict the behaviour of this variant of lobular carcinoma. PMID: 10672061

  • in the Egyptian population, p53 immunoreactivity appears to be an early event in cervical neoplasm, and seems to play an important role together with other cell regulatory proteins in the process of carcinogenesis, which could be different between sqcc and adenocarcinoma. PMID: 10607922

  • Immunohistochemical detection of p53 protein could improve the management of some patients with Barrett esophagus and mild histologic alterations. PMID: 10583932

  • the clinico-pathological correlations showed that p53 immunohistochemical expression is significantly associated with a poorer response to intensive chemotherapy. PMID: 10440751

  • Clinical failure is more common in the group of prostate cancer patients with abnormal p53 immunoreactivity. PMID: 10220791

  • p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer. PMID: 9815551

  • Immunohistochemically detected p53 protein status in NSCLC patients may be a promising indicator in determining in vitro chemosensitivity to some anticancer drugs, especially 5-Fu and ADM. PMID: 9610658

  • overexpression of p53 protein may play an important role in tumor progression from noninvasive to invasive in some breast carcinomas and may have potential as an indicator for poorer prognosis. PMID: 9568057

  • localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation. PMID: 12114668

  • Assay of p53 by immunohistochemistry in endoscopic biopsy specimens and brushings is an easy and reliable technique to assess p53 status in gastric carcinoma, and thus could serve as a marker to foresee the prognosis in these patients and assist in the diagnosis of malignancy before surgery. It may also be a valuable marker in screening patients with high risk of gastric carcinoma. PMID: 9594341

  • Serum determination of cytoplasmic p53 antigen can reveal this oncoprotein in the early stages of cancer, or even foretell its development. PMID: 9378162

  • p53 overexpression may be involved at an early stage in cervical carcinogenesis. PMID: 9066664

  • the immunohistochemical detection of p53 overexpression in biopsy specimens of bronchial epithelium might be useful for evaluation of preneoplastic lesions in high-risk group individuals and for early diagnosis of bronchial cancer. PMID: 9043024

  • in epithelial ovarian malignancies tumours showing p53 aberrations are significantly less sensitive to chemotherapy and more aggressive than those with functional p53. Thus, a routine analysis of this gene could have profound implications for the treatment of ovarian cancer. PMID: 9010031

  • Detection of immunoreactivity for p53 oncoprotein appears to be of real value in deciding the prognosis of transitional cell carcinoma of the upper urinary tract (TCC-UUT). PMID: 8958308

  • overexpression of p53 protein is one of the familial factors that correlates with carcinogenesis in the stomach. PMID: 8691838

  • The presence of p53 immunoreactivity as a compact pattern supports the idea that mutations of the p53 gene are early events in the sequence from dysplasia to invasive squamous-cell cancer of the skin. PMID: 8682583

  • p53 immunopositivity strongly correlates with recurrence/metastasis in Wilms' tumors. Furthermore, the accumulation of p53 in these tumors is not only due to mutations but may also involve stabilization of normal p53 with other proteins. PMID: 8623926

  • immunohistochemical expression of p53 protein in Wilms' tumour, presumably a result of mutation in the p53 tumour suppressor gene, correlates with histological classification, histological categorisation being one of the useful features in the prognostic assessment of Wilms' tumours. PMID: 8838120

  • The detection of p53 in non neoplastic tissue and the absence of a significant correlation between p53 expression and degree of differentiation support the hypothesis that the p53 gene mutation is involved in early stages of hepatocellular carcinogenesis. PMID: 8927568

  • p53 gene mutation is an early event in thymic tumorigenesis, and the p53 protein-positive cells increase with the progression of the tumor. Immunostaining reactivity of p53 may be a useful adjunct to differentiate thymic carcinoma from thymoma. PMID: 7572785

  • The p53 overexpression is present in advanced stage of colorectal carcinomas, thus demonstrating the prognostic value of this marker. PMID: 9455363

  • immunohistochemically strong p53 protein expression (more than 30% of tumor cells) has value in estimating a prognosis for patients with colorectal adenocarcinomas. PMID: 8527043

  • p53 expression in breast carcinomas means a significantly worse prognosis for grade II tumors (overall survival, P = 0.0002; disease-free period, P = 0.0116). PMID: 7705708

  • p53 expression takes place in the late stage of tumor progression and is related to the high malignant potential of hepatocellular carcinoma (HCCs). PMID: 7890286

  • mutation of the p53 gene may be involved in prostate cancer carcinogenesis. p53 reactivity marks an aggressive subset of prostate cancer and appears to be an independent prognostic indicator that is particularly valuable among the low to intermediate grade cancers. PMID: 7821906

  • Positive p53 immunostaining in renal cell carcinoma is associated with metastatic disease and poor survival in patients with early-stage disease. PMID: 8089867

  • the accumulation of p53 protein to immunohistochemically detectable concentrations is not a feature of low-grade cancer. This finding implies that abnormal p53 accumulation might be involved in the process of prostatic cancer progression. PMID: 8072122

  • p53 mutations play an important role in carcinogenesis in gastric carcinoma and further implies that p53 mutation may be an early occurrence during tumor transformation. PMID: 7892045

  • p53 may be involved in the development of more aggressive types of intracranial tumours. According to these results, p53 immunohistochemical positivity may serve as a prognostic marker in high-grade astrocytomas. PMID: 7826609

  • immunohistochemical p53 suppressor gene protein expression analysis has both diagnostic and prognostic value. PMID: 7928055

  • immunohistochemical detection of p53 protein proved useful in the diagnosis of malignant hemangioendothelioma. PMID: 7915452

  • mutant p53 protein may serve a prognostic role in a subset of cases of invasive ductal mammary carcinoma. PMID: 8379528

  • initially p53-negative tumors and initially p63-positive tumors that retain this labeling pattern may follow less aggressive biological courses and present better prognoses. PMID: 17499344

  • p53 is expressed late in carcinogenesis (14%) and as such, may be considered as an indicator of transformation of premalignant into malignant lesion. PMID: 17489760

  • Mutations of p53 were associated with lymph node metastases and III/IV stage of tumors that are signs of unfavorable prognosis in colorectal cancer. PMID: 17447881

  • serum p53-Ab was useful to predict a risk of early recurrence after curative surgical resection for esophageal squamous cell carcinoma (ESCC). PMID: 17439594

  • The data on p53 abnormalities, when considered separately, could be of relative value for predicting the behavior of gastric tumors. However, our analyses showed that studying p53 overexpression, loss of heterozigosity, microsatellite instability, and mutational analysis could provide data that, particularly in combination with some clinicopathological features, might be of clinical value for predicting the tumor behavior and patient response to therapy. PMID: 17436385

  • p53 overexpression is associated with a larger number of metastases and is correlated with a poor outcome as well as decreased intensity in p63 immunoexpression. PMID: 17391296

  • an increased anti-p53 antibodies positive rate for patients with gastric carcinoma and provided a useful marker for clinical diagnosis for patients with gastric carcinoma. PMID: 17292563

  • p53 overexpression is a common predictor of LR following treatment for all stages of primary operable ductal carcinoma of the breast. This marker may help in planning optimal treatment and follow-up. PMID: 17291532

  • The specificity of p53 mutation for pancreatic cancer is very high. Our results indicate that p53 gene mutation may provide an additional tool in differential diagnosis of CP (chronic pancreatitis) and PA (pancreatic adenocarcinoma). PMID: 16995472

  • p53 protein accumulation is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in hormone receptor-positive metastatic breast cancer. PMID: 16869955

  • p53 accumulation is believed to be an early event in neoplastic progression of the tongue. PMID: 16847809

  • p53 protein accumulation and nonpolymorphic intronic changes in p53 are associated with increased risk of progression to breast cancer in women with benign breast disease. PMID: 16835330

  • Clinical evidence that the p53 family is frequently overexpressed in lung cancer specimens, especially deltaNp63 in squamous cell carcinoma, was provided. The expression of deltaNp73 may be a useful marker for predicting a poor prognosis in resectable lung cancer. PMID: 16827107

  • serum concentration of p53 protein may be a convenient and useful non-invasive screening test for prediction of Hepatocellular carcinoma (HCC). PMID: 16681440

  • p-53 is a marker for premalignant lesions and helps in selecting patients for constant monitoring, upon the clinical verification of these results. PMID: 16624193

  • p53 protein transduction therapy may be a promising method for the treatment of bladder cancer. PMID: 16310931

  • p53 overexpression is associated with age, hormonal status, FIGO stage, and recurrence in uterine cervical carcinoma. PMID: 16289387

  • p53 mutations are present in typical keratinizing carcinomas, precursor lesions and disorders with elevated risk for vulvar cancer. Thus, p53 mutation seems to occur early in vulvar carcinogenesis and may become a useful marker, especially in lesions with increased risk of carcinoma. PMID: 16033093

  • p53 alteration can be considered, in primary endometrial carcinoma, an independent indicator for a moderate prognosis. PMID: 15678853

  • P53 protein is a reliable marker in identification of renal tubular injury. PMID: 15551735

  • nuclear p53 protein expression may represent an adverse prognostic marker in inflammatory breast cancer (IBC) and may provide a valuable tool for selecting treatment for this aggressive disease. PMID: 15448010

  • Presence of overexpression of oncoprotein p53 on borders of resection with aspects of dysplasia of various degrees seems, therefore, a marker of high risk of tumour progression and recurrence. PMID: 15198048

  • p53 mutation is an independent pre-treatment factor in stage II and III colorectal cancer after curative resection. PMID: 15172127

  • p53 overexpression is strongly related to poor prognostic indicators in endometrial adenocarcinoma. PMID: 12807239

  • Overexpression of p53 may serve as a marker for malignant transformation of inverted papilloma. PMID: 12779261

  • p53 expression was related to the clinical behavior of adrenal cortical tumors (ACT) in both children and adults and these findings seem to support a role for p53 in ACT progression. PMID: 12532223

  • Immunoreactivity of p53 is an independent factor for lymph node metastasis. The association of positive p53 with positive HPV DNA was related to a worse prognosis. PMID: 12050497

  • p53 expression seems to be a useful prognostic marker for breast sarcoma. PMID: 12002339

  • the presence of serum p53 autoantibodies is associated with decreased survival for patients with oesophageal carcinoma. PMID: 11911308

  • p53 overexpression was an independent predictor of recurrent disease in endometrial cancer. HER-2/neu overexpression had a more limited effect but enhance the effect of p53. PMID: 11516808

  • In patients with RCC, significant correlations between p53 protein expression and tumour stage, grade and survival time were observed. PMID: 11291681

Review Articles

  • p53 in breast cancer: mutation and countermeasures. PMID: 17485365

  • Reactivation of mutant p53: molecular mechanisms and therapeutic potential. PMID: 17401433

  • Structure-function-rescue: the diverse nature of common p53 cancer mutants. PMID: 17401432

  • Mutant p53: an oncogenic transcription factor. PMID: 17401430

  • Transcription regulation by mutant p53. PMID: 17401429

  • Interactions of mutant p53 with DNA: guilt by association. PMID: 17401427

  • Crippling p53 activities via knock-in mutations in mouse models.