We studied the incidence, clinicopathological relevance and prognostic significance of serotonin immunoreactive cells in a clinically well-documented series of 300 large bowel cancer patients. Serotonin immunoreactive cells were detected in 8 per cent of the carcinomas, occurring either as focal clusters (4.7 per cent) or as occasional single cells (3.3 per cent). Both types frequently displayed presence of mucin and/or immunoreactivity for secretory component as well. In respect of localization, stage or tumour extension and histological grade tumours with serotonin immunoreactivity showed no significant differences in comparison with carcinomas lacking this feature. In terms of survival, however, the tumours with serotonin immunoreactivity demonstrated a more aggressive clinical course in comparison with tumours without these cells. This phenomenon reached borderline statistical significance. It is therefore concluded that the study of serotonin immunoreactivity in large bowel carcinomas enables the identification of a subpopulation of colorectal carcinomas with a relatively poor prognosis.

We used the nude mouse tumour xenograft model to study the pathogenesis of mucosa alterations in the large bowel surrounding a carcinoma. In mouse colonic mucosa overlying HT-29 colonic carcinoma xenografts in the caecum, the crypts were elongated in comparison with those in distant mucosa and also frequently showed a shift towards sialomucin production. These features, which are comparable with socalled transitional mucosa (TM) in man, were absent in control animals inoculated with Indian Ink instead of HT-29 cells. Although the localization of the proliferative cell compartment in mouse colonic mucosa overlying HT-29 xenografts appeared to be confined to the lower half of the crypt as in normal mucosa, the relative length of the DNA synthesizing cell compartment along the crypts was slightly elongated. These data strongly suggest that TM should be regarded as a secondary phenomenon rather than a premalignant change in large intestinal epithelium and that higher proliferative activity of epithelial cells contributes little to the elongation of crypts in TM.