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)

This study was undertaken to assess the value of flow cytometric measurements of total p53 protein content and proliferation indices derived from in vivo halogenated pyrimidine labelling. Two series of colorectal cancer specimens were studied for which clinical outcome data were recorded. A series of 84 archival, ethanol-fixed, bromodeoxyuridine (BrdUrd) labelled colorectal tumours were analysed by flow cytometry for their total and cell cycle phase p53 protein content using the pAb1801 monoclonal antibody. A second series of 33 freshly obtained tumours was used for assay evaluation and for comparison with the archival material. In the archival series (n=84), the median p53-pAb1801 LI was 81.9% (range: 11.1-99.8%). In only three tumours could significant amounts of p53 protein not be detected. The median phase specific p53-pAb1801 LI in G0/G1 was 71.6%, in S was 95.5%, and in G2/M was 98.5%. In the series of fresh tumours (n=33), the median p53-pAb1801 labelling index (LI) was 94.6% (range: 17.9-99.9%). Only two tumours failed to express significant amounts of p53 protein. There was no significant difference in the generally high levels of p53 protein content between the fresh and archival series. Life-table analysis of the patients in the archival series failed to demonstrate a statistical difference in life expectancy in relation to Dukes' stage when tumours were stratified by the median total p53 labelling index. In this study, p53 content and proliferative indices measured by flow cytometry do not have independent predictive value over Dukes' grading in determining the outcome of colorectal cancer. Flow cytometry is confirmed as a practical tool for multi-parametric and cell cycle analysis of oncoprotein expression in human tumour biopsies.
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PMID:The flow cytometric analysis of total p53 protein content and proliferation indices in colorectal cancer, in relation to clinical outcome. 890 95

This study aimed to investigate whether immunohistochemical staining for nm23-H1 protein in the primary tumour is correlated with tumour stage, tumour differentiation, DNA ploidy, cell proliferative index, p53 status and patient survival time in colorectal cancer. Full-cross colorectal cancer biopsies were collected from 202 consecutive surgical specimens between 1987 and 1990. Immunohistochemical expression of nm23-H1 protein was investigated in cryosections, using a monoclonal anti-nm23-H1 antibody (clone NM 301). The staining pattern was classified as follows: strong homogeneous intensity, moderate homogeneous intensity, moderate focal intensity, or as negative. Immunohistochemical expression of p53 was investigated using a monoclonal anti-p53 antibody (DO-7). The DNA ploidy and cell proliferative index were determined by flow cytometry. Possible correlation between nm23-H1 staining patterns and the other studied tumour characteristics was explored at the end of 1994. Median survival time of living patients was 66 months, range 50-93 months. No correlation was found between various nm23-H1 staining patterns and tumour stage, cell proliferative index or p53 status. Nm23-H1-negative tumours and tumours with moderate focal staining intensity were less differentiated than tumours with strong homogeneous or moderate homogeneous staining intensity (P < 0.05). Of the nm23-H1-negative tumours, a significantly higher number was near-diploid rather than aneuploid, as compared with those expressing positive nm23-H1 (P < 0.05). The number of dead patients in Dukes' stages B and C did not correlate significantly with the nm23-H1 staining pattern. The nm23-H1 staining pattern alone, or combined with either of the other explored tumour characteristics, did not correlate with patient survival time. Immunohistochemical studies of the nm23-H1 protein expression are of minor value in the staging and prognostic prediction of colorectal cancer.
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PMID:NM-23 H1 immunohistochemistry is not useful as predictor of metastatic potential of colorectal cancer. 891 37

The prognostic significance of nuclear and cytoplasmic p53 protein, detected immunocytochemically using CM1 and PAb 1801 antibodies, was evaluated in right-sided and left-sided colorectal adenocarcinomas from 293 patients. CM1 nuclear and cytoplasmic p53 accumulation occurred in 38 and 25% of cases, respectively. PAb 1801 nuclear staining occurred in 18%, with no cytoplasmic staining. CM1 expression either in the nucleus or in the cytoplasm was positively related to PAb 1801 expression (P < 0.001 and P = 0.009, respectively). The incidence of CM1 nuclear and cytoplasmic expression was more frequent in right-sided tumours (P = 0.023 and P = 0.034, respectively), while PAb 1801 nuclear staining was more common in left-sided tumours (P = 0.011). In survival analyses, CM1 nuclear overexpression in the right-sided tumours (P = 0.016) and CM1 cytoplasmic overexpression in left-sided tumours (P = 0.04) were prognostic indicators, independent of Dukes' stage, DNA ploidy, PAb 1801 expression and each other. Further analysis showed that the prognostic value of CM1 nuclear expression was greater in right-sided tumours than in left-sided tumours (P = 0.018). The nuclear and cytoplasmic p53 protein detected with CM1 and PAb 1801 may play different roles in tumour progression and provide prognostic indicators for right- and left-sided colorectal tumours.
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PMID:Prognostic significance of p53 nuclear and cytoplasmic overexpression in right and left colorectal adenocarcinomas. 894 82

P53 is a tumor suppressor gene that has been implicated in the pathogenesis of a wide range of tumor types including colorectal cancers. bcl2 is a proto-oncogene that inhibits apoptosis. Immunostaining for P53 and BLC2 protein product was performed in a retrospective series of 80 colorectal carcinomas with a minimum follow-up of 5 years. The aim of the study was to evaluate the prognostic significance of P53 and BCL2 protein expression and their correlation with clinicopathologic variables such as pathologic disease stage (Dukes system), histologic grade, and vascular invasion. The patients were 41 to 76 years of age, and the follow-up ranged between 5 and 10 years. Among the 80 cases, 30 were Dukes stage A and 50 stage B. We found vascular invasion in 21.2%. P53 and BCL2 expression was detected, respectively, in 30.0% and 8.8%. We concluded that the P53 and BCL2 expression detected by immunohistochemistry in routinely processed, paraffin-embedded tissues: (1) has no prognostic significance; and (2) was not correlated with pathologic disease stage, histologic grade, or vascular invasion. Nevertheless, the number of patients in our study was small, and we believe that investigation of a larger series of patients is indicated.
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PMID:Prognostic markers for colorectal cancer: expression of P53 and BCL2. 899 81

The expression of the p53 and Rb1 proteins was examined in an unselected consecutive series of 250 primary operable colorectal carcinomas with a mean follow-up of 4.3 years (range 43-77 months). The overall cancer-specific mortality was 34.8%, with 87 cancer deaths and 35 deaths as the result of other causes. Expression of p53 protein was identified in 152 of 250 (60.8%) cases, with expression of Rb1 protein in 207 of 250 (82.8%) cases. There was no association of p53 or Rb protein expression with patient age, sex, tumour site, tumour size, tumour type, tumour grade, peritumoral fibrosis, tumour lymphocytic infiltrate, nature of the tumour margin, extramural vascular invasion, number of lymph nodes or high apical lymph node involved or local peritoneal infiltration by tumour, Dukes' stage or Jass group. There was no difference in overall survival or recurrence-free survival for those cases that showed p53 expression or Rb1 protein expression compared with those cases showing absence of p53 or Rb1 protein expression, although patients with tumours showing aberrant (reduced) Rb1 protein expression demonstrated shorter recurrence-free survival and overall survival. The effect of 'aberrant' Rb1 protein expression and shorter recurrence-free and overall survival did not, however, achieve independent statistical significance. The results from this study would suggest that expression of p53 and Rb1 proteins does not appear be useful in determining the prognosis of operable colorectal cancer.
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PMID:p53 and Rb1 protein expression: are they prognostically useful in colorectal cancer? 900 Jun 3

Abnormalities in the p53 tumour suppressor gene and in the expression of its protein are common in colorectal carcinoma. The prognostic significance of these p53 abnormalities was studied in 66 patients with colorectal cancer, followed for more than 10 years. Single-strand conformation polymorphism (SSCP) analysis was used to detect alterations in exons 5-8 of the p53 gene. Paraffin sections were examined immunohistochemically for p53 overexpression with the monoclonal antibody DO-7 (Dako) both with and without microwave antigen retrieval. Abnormalities of the p53 gene were found in 41 per cent of cases by SSCP analysis. Outcome was unrelated to SSCP abnormalities (P = 0.19), except for the Dukes' A and B subgroup, where decreased survival was found in cases with abnormal SSCP (P = 0.01). Overexpression of p53 protein was seen by immunohistochemistry in 47 per cent of cases without, and in 52 per cent of cases with microwave antigen retrieval. Immunohistochemical overexpression of p53 protein either with or without microwave antigen retrieval was an independent prognostic indicator of poor survival. These results suggest that for routine purposes, immunohistochemical detection of the p53 protein product may be more useful than SSCP analysis of the encoding p53 gene in identifying those at high risk of colorectal cancer recurrence and death.
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PMID:Prognostic significance of p53 abnormalities in colorectal carcinoma detected by PCR-SSCP and immunohistochemical analysis. 901 55

We analysed the frequency of p53 mRNA overexpression in a series of 109 primary colorectal carcinomas and its association with p53 gene mutation, which has been correlated with short survival. Sixty-nine of the 109 cases (63%) demonstrated p53 mRNA overexpression, without any correlation with stage or site of disease. Comparison with p53 gene mutation indicated that, besides cases in which p53 gene mutation and p53 mRNA overexpression were either both present (40 cases) or both absent (36 cases), there were also cases in which p53 mRNA was overexpressed in the absence of any mutation (29 cases) and those with a mutant gene in which the mRNA was not overexpressed (four cases). Moreover, the mutant p53 tumours exhibited an increase of p53 mRNA expression, which was significantly higher in tumours expressing the mutated allele alone than in tumours expressing both wild- and mutated-type alleles. These data (1) show that p53 mRNA overexpression is a frequent event in colorectal tumours and is not predictive of the status of the gene, i.e. whether or not a mutation is present; (2) provide further evidence that p53 protein overexpression does not only result from an increase in the half-life of mutated p53 and suggest that inactivation of the p53 function in colorectal cancers involves at least two distinct mechanisms, including p53 overexpression and/or mutation; and (3) suggest that p53 mRNA overexpression is an early event, since it is not correlated with Dukes stage.
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PMID:Overexpression of p53 mRNA in colorectal cancer and its relationship to p53 gene mutation. 905 5

p53 overexpression was studied by immunohistochemistry in 96 consecutive colorectal cancer patients, subdividing positive specimens according to two staining patterns: cytoplasmic or nuclear. Forty-seven per cent of the cases were p53 positive, a significant correlation being found with Dukes' stage (P = 0.0036). A prevalence of nuclear staining was observed in Dukes' B and cytoplasmic in Dukes' D stages. After 36 months, 23% of the patients had a recurrence, and 45% were p53 positive, all Dukes' C-D stage with cytoplasmic staining. The Kaplan-Meier curve showed a significant correlation between p53 cytoplasmic staining and disease-free survival period (P = 0.002). With respect to disease-free survival, the Cox proportional hazard regression test, comparing p53 positivity with Dukes' stage, showed the latter to be the most significant variable. In our series of patients, advanced Dukes' stage tumours were localised in the right colon, where a higher percentage of p53 positivity (67% versus 40% of the left side), as well as a higher frequency of cytoplasmic staining was observed. In conclusion, from the data obtained, a strong correlation between p53 cytoplasmic staining and patient prognosis is clearly indicated.
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PMID:Prognostic significance of cytoplasmic p53 overexpression in colorectal cancer. An immunohistochemical analysis. 908 57

In both the primary tumor and associated lymph-node metastases of 40 cases of Dukes' C colorectal adenocarcinomas, exons 5 to 9 of the p53 tumor-suppressor gene were examined by PCR amplification and single-strand-conformation-polymorphism(SSCP) analysis. Mobility shifts indicating p53 mutations, which were confirmed by direct sequencing, were identified in 14 primary cancers (35%) and in 19 of the 40 lymph-node metastases (48%). In 12 cases (30%), the p53-mutation status in the primary cancer and its lymph-node metastases was identical. This result is compatible with the hypothesis that when a p53 mutation occurs before the establishment of lymph-node metastasis, it subsequently persists in the metastatic nodes. In 7 cases (18%), p53 mutations were identified in lymph-node metastases that were not concordant with the p53 status in the primary tumor. This finding can be explained by assuming that (1) p53 heterogeneity existing in the primary tumor is not reflected in all metastases and/or (2) new p53 mutations may occur during the development of metastatic lesions.
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PMID:Genetic diversity at the p53 locus between primary human colorectal adenocarcinomas and their lymph-node metastases. 909 48

Colorectal cancer has been studied from the point of view of the relationships between several variables, including proliferative activity and p53 protein expression. However, stereologic evaluation of nuclear size has not been thoroughly described. In the present study, measurements of the volume-weighted mean nuclear volume (nuclear Vv), have been performed in well, moderately and poorly differentiated colorectal adenocarcinomas and correlated with the Dukes' stage and other factors such as proliferative activity and p53 protein immunoreactivity. Although the mean values of nuclear Vv were higher in poorly differentiated cancers or Dukes' C&D stage than in well and moderately differentiated tumors or Dukes' A&B stage, these differences were not significant. However, the variability of nuclear size in colorectal cancers was more relevant than the mean values of nuclear Vv with respect to their invasive classification. The carcinomas which extended beyond the serosa (Dukes' stage C&D) had higher biologic variation than those grouped as Dukes' stage A&B. The results of the present study also indicate that nuclear size in colorectal cancers has a positive correlation with both proliferative activity and p53 protein expression. The relationship between nuclear Vv and proliferative activity emphasizes the possible prognostic relevance of this stereologic estimate of nuclear size in colorectal adenocarcinoma.
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PMID:Stereologic estimates of volume-weighted mean nuclear volume in colorectal adenocarcinoma: correlation with histologic grading, Dukes' staging, cell proliferation activity and p53 protein expression. 926 6


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