Abnormalities of the p53 gene have been identified in many malignancies, with reports of aberration in over half of colorectal, lung, breast and hepatocellular carcinoma cases. The normal gene acts as a recessive oncogene, while mutations change the apparent function to that of a dominant oncogene. In this investigation a 3-layered immunoperoxidase technique was applied to routinely fixed and paraffin-embedded tissue sections from 125 gastric carcinomas, using a polyclonal anti-p53 antibody (CM-I). We found that 57% of these carcinomas expressed high levels of p53 protein (positive nuclear staining). Survival analysis revealed a strong association between p53 status of the tumour and patient survival time after diagnosis (p = 0.02, Mantel-Cox Test); odds ratio of death, 2.09 (95% confidence interval 1.02 to 4.25). The 5-year survival of patients with p53-expressing tumours was 24%, compared with 56% for those non-p53-expressing tumours (the median survival times were 13 and 102 months, respectively).
Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency ofp53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p=0O006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%
The material was taken from surgical specimens of large intestine resected for carcinoma. A parallel study by electron microscopy and mucin histochemistry was made on fragments from “transitional” (TR) mucosa (adjacent to carcinoma) and “normal” (N) mucosa (remote from the tumor). These were compared with similar studies on the mucosa from control individuals. Histochemically, the “TR” mucosa shows an increase in sialomucins as compared with the “N” and control mucosae, where sulphomucins normally predominate. At the ultrastructural level, the “TR” mucosa is characterized by the following changes which may precede the histochemical variations: A) alteration in the relative proportions of the different cell types, along the crypt, with a persistence of immature and intermediate cells at higher levels of the crypt than in the control. Mature absorptive cells are fewer and bear an inverse relationship to intermediate cells. Goblet cells are increased in number and size. B) Appearance of electron‐dense bodies 0.15–0.3μm in diameter and membrane limited. C) An elaborated and enlarged Golgi zone showing increased secretory activity. It is suggested that mucin and ultrastructural changes described in the “TR” zone may indicate a failure in the normal process of cell differentiation along the crypt. Previous work7,8 further suggests that the mucin changes may be primary, reflecting a cellular response to unknown stimuli (i.e., carcinogens) rather than a local secondary effect of tumor growth. As for the ultrastructural features in the “TR” mucosa, the secondary effect cannot be excluded at the present.
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