P53 Tumor Suppressor Gene Protein Research Articles

The prognostic significance of the accumulation of p53 tumour-suppressor gene protein in gastric adenocarcinoma

We have studied the expression of p53 in 206 patients with gastric adenocarcinomas. A standard immunohistochemical technique employing the CM-1 anti-p53 polyclonal antibody was applied to the routinely fixed and paraffin-embedded material from these tumours; overexpression of p53 was defined as positive nuclear staining: 46% (94/206) of gastric carcinomas expressed high levels of p53. There was no significant correlation between p53 positivity and the tumour grade, growth pattern, the Lauren type or lymph node metastases. Correlation with disease stage was only marginally significant (P = 0.05). Life table analysis revealed a highly significant association between p53 expression and survival (P = 0.0062), the odds ratio of death being 1.89 (95% confidence interval 1.33-2.69). The overall 5-year survival of patients with p53-positive tumours was 3% compared with 16% for those with p53-negative tumours (median survival time being 5.6 and 11.4 months respectively). These data suggest that overexpression of the p53 oncoprotein is an independent marker of shortened survival in gastric cancer patients.

Retinoblastoma and p53 tumour suppressor gene protein expression in carcinomas of the thyroid gland.

One hundred and thirty-one thyroid tumours were examined immunohistochemically for expression of retinoblastoma (RB) and p53 protein. The results demonstrate that RB protein is not lost in any cases, indicating that inactivation of the RB gene is unlikely to play a central role in the pathogenesis of thyroid tumours. Eighteen of 24 (75 per cent) undifferentiated carcinomas, 6 of 32 (19 per cent) papillary carcinomas, 5 of 29 (17 per cent) follicular carcinomas, and 6 of 46 (13 per cent) medullary carcinomas showed p53 protein nuclear staining. In 46 per cent of the undifferentiated carcinomas many of the tumour cells had accumulated p53 protein, whereas in the other positive cases less than 5 per cent of the cells had increased p53 protein levels. Our results strongly suggest that p53 protein abnormalities play a crucial role in the progression of well-differentiated to undifferentiated thyroid carcinomas.

Elevated levels of the p53 tumour suppressor protein in the basal layer of recurrent laryngeal papillomas

Using immunocytochemical techniques, recurrent laryngeal papillomas from six adult patients were studied. The p53 tumour suppressor gene protein was detected in the basal epithelial cells in papillomas from all six patients. None was detected in normal epithelium. Elevated levels of p53 protein are usually indicative of its inactivation either by point mutation or by complexing with tumour virus proteins.

Accumulation of p53 Tumor Suppressor Gene Protein: An Independent Marker of Prognosis in Breast Cancers

Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. IgG1 monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas--21 sporadic and 76 familial (hereditary)--from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. Immunohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation.