Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the expression of p53 in 82 formalin-fixed, paraffin-embedded archival tissue specimens of lip and intraoral squamous cell carcinomas (SCCs) from the period 1930-1995, by immunohistochemistry using three monoclonal antibodies (MAbs DO-7, DO-1 and 1801). Before incubation, sections were pretreated with 0.1% Protease enzyme at 37 degrees C for 10 min followed by 5 + 5 min microwave oven heating at 700 W and 425 W, respectively. Formalin-fixed tissues of 10 carcinomas of the uterine cervix positive for p53 were used as controls. With one or more of the three MAbs, p53 was expressed in 73% of the 82 SCCs examined. With only protease enzyme pretreatment or microwave oven heating, p53 was expressed in 9/82 and 12/82 of the SCCs, respectively. Of the 82 SCCs, 60%, 45% and 23% expressed p53 with DO-7, DO-1 and 1801, respectively. The kappa coefficient indicated poor agreement between these results for the antibodies, and for lip and intraoral SCCs, except for p53 expression in intraoral SCCs demonstrated by DO-1/1801, which showed fair agreement. The present study suggests that combined protease pretreatment and microwave oven heating of tissue sections improved unmasking of p53 antigenic sites in archival material stored for up to 65 years.
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PMID:Immunohistochemical detection of p53 in archival formalin-fixed tissues of lip and intraoral squamous cell carcinomas from Norway. 936 90

In HBV related hepatitis it is generally accepted that the liver injury is mediated by an immune response to the virus, since HBV is not directly cytopathic. The first step in cytotoxic T lymphocyte mediated immune reaction in HBV infected mice is the induction of apoptosis. The role of BCL-2, p53 and PCNA (as the main regulators of cell cycle homeostasis) in this process has not been studied. The aim of this pilot study is to estimate immunohistochemically the expression of the BCL-2, p53 and PCNA in a group of HBV infected patients at various stages of the disease. Formalin fixed, paraffin embedded liver biopsies from 5 patients with HBsAG positivity in their serum were used for immunohistochemical study of the expression of BCL-2, PCNA (PC10) and P53 (DO1clone). As the chromogen we used both the DAB and AEC. The results were co-related with the 3 liver biopsies as controls. In the hepatocytes of the all cases (including controls) we did not found any positivity of BCL-2, p53 and PCNA. However the majority of the lymphocytes present in the liver of some cases of HBV infected patients were strongly BCL-2 positive. This preliminary results of very small group of patients could indicate that hepatocytes in the HBV infection are in the quiescent stage as in the controls and that the cell cycle regulation during infection could be controlled by other genes such as bax, bcl-Xs, FAS etc., but further studies are required.
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PMID:Immunohistochemical study of the expression of BCL-2, PCNA and P53 proteins in the patients with hepatitis B. The pilot study. 943

Cystatin A (acid cysteine proteinase inhibitor; ACPI) is a natural inhibitor of cysteine proteinases. It has been suggested that an inverse correlation exists between cystatin A and malignant progression. We wanted to assess the biological and clinical significance of cystatin A in infiltrative breast carcinoma by immunohistochemical staining. Formalin-fixed paraffin-embedded material from 440 cases treated during the years 1988-1991 was used in the study. After exclusion of patients with disseminated disease at diagnosis, previous contralateral breast carcinoma, and absence of follow-up data, 384 patients could be included in the survival analysis. For immunohistochemical analysis of cystatin A, we used monoclonal cystatin A antibody WR-23/2/3/3, the binding of which was detected by the avidin-biotin-peroxidase method. Immunohistochemical analysis of Bcl-2 and p53 was also done, and mitotic activity was evaluated. Positive staining for cystatin A was found in 52 of 440 cases. The staining was irregular but showed irrefutably positive areas within neoplastic tissue. Most of the positive tumors were of the ductal infiltrative type, but two were mucinous carcinomas, one medullary and one squamous cell carcinoma. No lobular carcinomas showed positive staining. Focal cystatin A positivity was seen in myoepithelial cells of benign ducts. Occasional apoptotic bodies within the neoplasm showed strong positivity for cystatin A. Tumors positive for cystatin A were of larger size and had higher mitotic activity than cystatin A-negative tumors. Cystatin A was associated with negative Bcl-2 staining, but there was no statistically significant association between axillary lymph node status or p53 immunostaining. The risk for breast cancer-related death was significantly higher in patients with cystatin A-positive tumors than in those with cystatin A-negative ones. The risk increase was significant also in lymph node-negative patients. After adjusting for the effect of tumor size, histological grade, and lymph node status, cystatin A-positive patients still had a higher risk of death. Patients with cystatin A and p53 coexpression had a higher risk of death than the other patients. The findings reveal a new variant of aggressive breast cancer. This type of carcinoma may develop during tumor progression through genetic instability that allows cystatin A expression and gives growth advantage to a clone of tumor cells.
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PMID:Cysteine proteinase inhibitor cystatin A in breast cancer. 945 85

Mutational alterations involving the p53 and retinoblastoma (RB) tumor suppressor genes are implicated in the oncogenesis of a variety of tumors. Their role in the pathogenesis of prostatic adenocarcinoma remains to be fully elucidated, and their detection in high-grade prostatic intraepithelial neoplasia (HG-PIN) has not been closely examined. We studied the immunohistochemical expression of RB and p53 proteins in HG-PIN, benign prostate, and prostatic adenocarcinoma from 25 radical prostatectomy specimens. Formalin-fixed, paraffin-embedded tissue sections pretreated with antigen retrieval in citrate buffer were stained with anti-RB antibody RB-WL-1 and anti-p53 antibody DO-7. RB immunoreactivity was present in all of the cases in the foci of HG-PIN, benign prostate, and prostatic adenocarcinoma. Mutant p53 protein was detected in 56% of HG-PIN, 72% of prostatic adenocarcinomas, and 20% of benign prostatic glands. A multivariate analysis of variance showed an overall difference in p53 immunoreactivity between HG-PIN, benign prostate, and prostatic adenocarcinoma (P < .001). There was a statistically significant difference between immunoreactivity of the benign prostate and of HG-PIN (P < .001) and between the immunoreactivity of benign prostate and prostatic adenocarcinoma (P < .001). The immunoreactivities of HG-PIN and prostatic adenocarcinoma were not statistically different (P = .3). These data suggest that RB loss might not play a role in initiation of all cases of prostatic adenocarcinoma. The p53 immunoreactivity in HG-PIN was significantly different from that found in benign prostate and was similar to that of prostatic adenocarcinoma. This is in keeping with the putative premalignant character of HG-PIN.
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PMID:Immunohistochemical expression of retinoblastoma and p53 tumor suppressor genes in prostatic intraepithelial neoplasia: comparison with prostatic adenocarcinoma and benign prostate. 952 70

Estimated vascular density obtained with the aid of antibodies against endothelial cells has been claimed to be an independent prognostic indicator for invasive ductal breast carcinoma. Since 1991 most studies have counted the number of vessels with the optic microscope. We have performed immunohistochemical staining for Factor VIII on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months, who had received postoperative chemoradiation therapy. We have performed a manual count with a 20x objective of the vessels in the vascular hot-spot identified in a 4x field. We analysed the association of this factor with epidemiological risk factors, histopathological features, hormonal receptor status and p53 and c-erbB-2 expression and the influence on prognosis. In univariate analysis vascular density is a significant prognostic indicator in both node-negative and node-positive patients, together with staging, Baak's morphometric multiparametric index, tumour size and histological grade. However, in multivariate analysis only tumour staging and vascular density are independent prognostic factors in breast carcinoma.
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PMID:Vascular density as a prognostic indicator for invasive ductal breast carcinoma. 958 76

Spontaneous proliferative lesions in the nasopharyngeal meatus were identified as the cause of death in 12 of 1,600 male and 5 of 1,600 female Fisher 344 (F344) rats used in 2-yr carcinogenicity studies; none of the lesions were considered treatment related. All the rats showed dyspnea, abdominal distension, and clinical deterioration. Gross features were characterized by simultaneous occurrence of conspicuous gaseous distension of the intestinal tract, especially in the ileum and cecum, and focal nodular lesions in the nasopharyngeal meatus. Histopathologically, the nasopharyngeal meatus was partially obstructed by the following proliferative lesions: 3 areas of hyperplasia of the ectopic sebaceous glands in the soft and hard palate, 4 areas of squamous metaplasia (SM) with massive hyperkeratosis, 5 squamous cell papillomas (SCPs), and 5 squamous cell carcinomas (SCCs). No pathological changes were found in the distended portion of the intestinal tract. Formalin-fixed, paraffin-embedded samples of the proliferative lesions from the nasopharyngeal meatus were examined for the presence of mutations in the c-H-ras and c-K-ras genes. In vitro amplification of DNA using a polymerase chain reaction was combined with a nonisotopic method for selective oligonucleotide hybridization. Two of the 4 SM lesions, 3 of the 5 SCPs, and 5 of the 5 SCCs contained 1-3 point mutations in the c-H-ras and/or c-K-ras gene. Immunohistochemically, overexpression of p53 protein was found in 1 area of SM with a dysplastic lesion and 2 SCCs. These findings indicate that detailed examination of the upper respiratory system, including the nasopharyngeal meatus, may be particularly helpful for identifying primary occult lesions in F344 rats that show only gut distension at necropsy in long-term toxicity studies. In addition, mutations of the ras genes may be an important step in the early stages of carcinogenesis in the rat nasopharyngeal meatus, whereas p53 mutations could occur relatively late.
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PMID:Spontaneous proliferative lesions in the nasopharyngeal meatus of F344 rats. 960 49

DNA mismatch repair is an important mechanism involved in maintaining the fidelity of genomic DNA. Defective DNA mismatch repair is implicated in a variety of gastrointestinal and other tumors; however, its role in hepatocellular carcinoma (HCC) has not been assessed. Formalin-fixed, paraffin-embedded archival pathology tissues from 46 primary liver tumors were studied by microdissection and microsatellite analysis of extracted DNA to assess the degree of microsatellite instability, a marker of defective mismatch repair, and to determine the extent and timing of allelic loss of two DNA mismatch repair genes, human Mut S homologue-2 (hMSH2) and human Mut L homologue-1 (hMLH1), and the tumor suppressor genes adenomatous polyposis coli gene (APC), p53, and DPC4. Microsatellite instability was detected in 16 of the tumors (34.8%). Loss of heterozygosity at microsatellites linked to the DNA mismatch repair genes, hMSH2 and/or hMLH1, was found in 9 cases (19.6%), usually in association with microsatellite instability. Importantly, the pattern of allelic loss was uniform in 8 of these 9 tumors, suggesting that clonal loss had occurred. Moreover, loss at these loci also occurred in nonmalignant tissue adjacent to 4 of these tumors, where it was associated with marked allelic heterogeneity. There was relatively infrequent loss of APC, p53, or DPC4 loci that appeared unrelated to loss of hMSH2 or hMLH1 gene loci. Loss of heterozygosity at hMSH2 and/or hMLH1 gene loci, and the associated microsatellite instability in premalignant hepatic tissues suggests a possible causal role in hepatic carcinogenesis in a subset of hepatomas.
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PMID:Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene loci occurs during hepatic carcinogenesis. 965 1

We have previously shown that metastatic carcinomas of unknown primary site overexpress several tumor markers as well as the products of the oncogenes c-myc, ras and c-erbB2. We analyzed the tissue expression of the protein products of the apoptosis modulation genes p53 and bcl-2 in 47 CUP cases. Formalin-fixed, paraffin embedded tumor specimens were stained with commercially available antibodies to p53 (DO7) and bcl-2 after antigen retrieval by the microwave method. Staining was evaluated by intensity (1+ to 3+), percentage of positive cells (1-100%), and the 'intensity times percentage' product defined as the immunoreactivity index with values ranging from 0 to 300. Immunoreactivity index values higher than 150 were considered to characterize protein over-expression. Expression of p53 was identified in 70.2% of tumors while 53% of them showed a high immunoreactivity index. Bcl-2 expression was detected in 65% of tumors and overexpressed in 40%. Overexpression of both proteins was detected in 20% of tumors. The detection of either protein was not associated with any of the major clinicopathological variables studied. Nevertheless, a trend towards a more favourable response to platin based chemotherapy was seen in the cases that showed a strong expression of both proteins, when analysed by immunoreactivity index and percentage of positive cells. We conclude that CUP overexpress at a high percentage the p53 and the bcl2 proteins. The observed weak association of strong expression of these proteins with response to platin-based chemotherapy deserves further evaluation in the CUP setting.
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PMID:Bcl2 and p53 protein expression in metastatic carcinoma of unknown primary origin: biological and clinical implications. A Hellenic Co-operative Oncology Group study. 967 43

Extranodal oral lymphomas, seen with increasing frequency in HIV infection, may have dysfunctional apoptotic mechanisms that favor tumor progression. The purpose of this study was to evaluate extranodal lymphomas from HIV-positive patients for expression of apoptosis-associated proteins. Correlations were made with 10 histologically comparable extranodal lymphomas from HIV-negative patients and 6 hyperplastic lymph nodes from otherwise healthy young adults. Formalin-fixed tissue sections were immunohistochemically stained for apoptosis-associated proteins (Bcl-2, Bcl-x, Bax, Bak, p53, MDM2, BHRF). In situ hybridization was also done on deparaffinized sections for Epstein-Barr virus EBER mRNA. Eighteen consecutive oral lymphomas were studied in HIV/AIDS-positive patients. Four of 5 intermediate-grade lymphomas expressed Bcl-2 to a greater degree than did high-grade lymphomas (4 of 13). Most lymphomas were positive for Bcl-x and Bax, and few expressed Bak. The staining patterns for these proteins were similar to those seen in HIV-negative patients. Staining patterns were relatively consistent in the hyperplastic lymph nodes, whereas such patterns were irregular in lymphomas. Positive p53 staining was seen in 11 of 18 HIV-positive cases; 9 of these were also MDM2-positive. Double stains suggested that both p53 and MDM2 proteins were expressed in the same cells in these nine cases. Epstein-Barr virus-EBER mRNA was detected in 14 of 18 cases and in 3 of 10 cases from HIV-negative patients. BHRF staining was evident in only a few cells of three HIV-positive lymphomas. The irregular expression of Bcl-2, Bcl-x, Bax, and Bak in oral lymphomas indicates dysfunctional apoptotic mechanisms in these tumors. Bcl-2 staining differs with tumor grade. Positive staining for p53 and MDM2 proteins is a notable feature of lymphomas in HIV-positive patients and may relate to binding of MDM2 to wild-type p53. Epstein-Barr virus is more commonly associated with oral lymphomas in HIV-positive patients, although the Epstein-Barr virus-produced protein BHRF, which has Bcl-2-like activity, is minimally expressed.
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PMID:Apoptosis-associated proteins in oral lymphomas from HIV-positive patients. 972 96

A better knowledge of the biological aggressiveness of individual tumors could facilitate the selection of treatment in prostate cancer patients. This study assesses the influence of histological and molecular features in core needle biopsy specimens of prostate cancer on tumor-specific survival. Formalin-fixed core needle biopsy specimens from 111 consecutive patients (mean follow-up, 5.0 years) were immunohistochemically examined for their proliferative activity (Ki67 labeling index [LI]) and expression of p53 and Bcl-2. Overexpression of p53 was found in 16% of the biopsy specimens and was mainly restricted to poorly differentiated tumors. Bcl-2 positivity was found in 20% of tumors. The median Ki67 LI was 7.5%. There was a strong relationship between Ki67 LI and Gleason grade, with a continuous increase in the proliferative activity from low-grade to high-grade tumors (P = .0006). Univariate tumor-specific survival analysis showed that high Gleason score (P = .0018), high percentage of biopsy tumor involvement (P = .0227), high Ki67 LI (P = .0007), and p53 positivity (P = .0024) were predictors of tumor-related death. A high Ki67 LI emerged as the only independent predictor of tumor-specific survival in multiparametric analysis. These results indicate that core needle biopsy specimens of the prostate not only are useful for diagnosis of malignancy but also can provide valuable prognostic information. Immunohistochemical examinations of molecular features may be a helpful adjunct for a better pretherapeutic assessment of prostate cancer aggressiveness and therefore contribute to an improved initial patient management.
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PMID:Ki67 labeling index in core needle biopsies independently predicts tumor-specific survival in prostate cancer. 974 10


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