The occurrence of endocrine cells in 350 cases of colorectal adenocarcinoma was studied by immunohistochemistry for chromogranin A (CGA). The hormone profile of endocrine tumor cells, the correlation between endocrine differentiation and presence of other colorectal epithelial-cell lineages and the prognostic relevance of endocrine differentiation in colorectal cancer were investigated. CGA-positive tumor cells were found in 30% of cases, 21% showing moderate positivity and 9.0% extensive positivity. Of CGA-positive tumors, 70% additionally produced neurohormones, mainly indigenous to normal colorectal epithelium: 55% showed immunoreactivity for glucagon-like substances, 20% for serotonin and 10% for somatostatin, PYY and HCG. No immunoreactivity was found for various neurohormones not normally produced by colorectal endocrine cells. CGA-positive tumors tended to be more aggressive than CGA-negative tumors. Especially, tumors with extensive CGA positivity showed shorter survival, which was most apparent within Dukes' stage C. In multivariate analysis, extensive CGA positivity was an independent indicator of poor prognosis. CGA immunoreactivity significantly correlated with mucin production, but not with expression of secretory component (SC), a columnar-cell marker. Mucin production significantly correlated with SC expression. Tumors positive for CGA but not for mucin and/or SC showed the worst prognosis. SC expression was a relatively favorable feature, and mucin-producing tumors showed intermediate behavior.

Background-There is a need for markers in colorectal cancer which will allow subclassification of stage groups into subgroups with high versus low risk of recurrent disease. Aims-To develop monoclonal antibodies that recognise antigens on immature crypt base cells, on the assumption that in a neoplasm undiVerentiated but not the terminally diVerentiated cells will be responsible for tumour progression. Methods-Colon crypt cells which were isolated from human colonic mucosa by EDTA/EGTA incubation were studied. By stepwise harvesting, crypt base cell enriched fractions were obtained, and after incubation with antibodies against dominant antigens, used as immunogens. Results-Of one crypt base cell specific antibody (5E9), the reactive epitope appeared to be a non-terminal carbohydrate in the mucin O-glycans of the colon. The epitope did not seem to be colon specific, but was expressed in a variety of other tissues. In colorectal carcinomas, 5E9 immunoreactivity identified a subgroup of patients with a tendency for worse prognosis. Conclusion-A mucin associated maturation epitope was identified in colonic crypt base cells, the expression of which in Dukes' stage B3 colorectal carcinoma may be associated with poor prognosis.