The expression of mucin MUC2 was investigated in normal colonic tissue, in colonic adenomas and in carcinomas of the mucinous and non-mucinous type. The latter were subdivided into carcinomas originating from the adenoma-carcinoma sequence (ACS) and de novo (DN) carcinomas. The expression was assayed by immunohistochemistry with the monoclonal anti-MUC2 antibody CCP58 and by mRNA semiquantitation. MUC2 protein epitope CCP58 was strongly expressed in 21% of normal colonic tissues, in 40% of villous and in 48% of tubular adenomas. Mucinous carcinomas exhibited strong expression in 72%, ACS carcinomas in 21% and DN adenocarcinomas in none of the tumors investigated. Compared with the adjacent non-malignant tissue (transitional mucosa), CCP58 epitope expression in the tumor was higher in 74% of mucinous carcinomas, but equal or lower in 69% of ACS carcinomas and in 100% of de novo carcinomas. The alterations of MUC2 expression detected by immunohistochemistry in adenocarcinomas were confirmed on mRNA level. These data indicate that the MUC2 expression pattern is different in the 3 carcinoma types investigated. MUC2 over-expression occurs in the adenomatous tissue. It is always maintained in mucinous carcinomas, but frequently decreased in non-mucinous ACS carcinomas. DN carcinomas are most frequently associated with decreased expression of MUC2.
Summary In order to determine the clinical value of CEA detection in large bowel cancer tissue the patterns rather than the intensity of immunoreactivity of CEA reactive antibodies were analyzed in 312 large bowel cancer patients especially in relation to patient survival. CEA immunoreactivity appeared to be distinguishable into a predominantly apical/cytoplasmic and a predominantly membranous pattern.Twenty-four (7.7%) tumours were found to be CEA negative or only focally positive. Two hundred and eighty-three (90.7%) of the carcinomas showed a predominantly apical/cytoplasmic immunoreactivity pattern, whereas 5 (1.6%) of the tumours revealed mostly membranous CEA immunoreactivity. CEA negative or focally positive carcinomas and CEA positive tumours with membranous immunoreactivity were significantly more often observed in the group of poorly differentiated carcinomas (P>0.001), but showed no significant correlation with stage of tumour extension (P=0.11). Also, these carcinomas demonstrated a more aggressive course in patients compared to CEA positive tumours with an apical/cytoplasmic CEA expression pattern. We, therefore, conclude that determination of the pattern of CEA immunoreactivity in large bowel cancer tissue may enable the detection of subgroups of patients with a poor prognosis.
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