Low tumour cell proliferation at the invasive margin is associated with a poor prognosis in Dukes' stage B colorectal cancers

The conflicting results about the prognostic impact of tumour cell proliferation in colorectal cancer might be explained by the heterogeneity observed within these tumours. We have investigated whether a systematic spatial heterogeneity exists between different compartments, and whether the presence of such a systematic heterogeneity has any impact on survival. Fifty-six Dukes' stage B colorectal cancers were carefully morphometrically quantified with respect to the immunohistochemical expression of the proliferative marker Ki-67 at both the luminal border and the invasive margin. The proliferative activity was significantly higher at the luminal border compared with the invasive margin (P < 0.001), although the two compartments were also significantly correlated with each other. Tumours with low proliferation at the invasive margin had a significantly poorer prognosis both in univariate (P = 0.014) and in multivariate survival analyses (P = 0.042). We conclude that Dukes' B colorectal cancers exhibit a systematic spatial heterogeneity with respect to proliferation, and tumours with low proliferation at the invasive margin had a poor prognosis. The present data independently confirm recent results from the authors, and provide new insights into the understanding of tumour cell proliferation in colorectal cancer. © 1999 Cancer Research Campaig

Immunohistochemical localization of a specificileal peptide in the pig

The tissue distribution of a polypeptide purified from pig ileal mucosa tentatively called porcine ileal polypeptide (PIP) and known to have potent acid secretagogue activity has been studied with immunohistochemical methods together with extraction of different tissues followed by radioimmunoassay for PIP content. Histochemically the peptide is found in superficial epithelial cells in the mucosa of the distal 20% of the small intestine and to some extent in the mucosa of the urinary tract. There is no staining of goblet cells or crypt cells. The staining in the urinary tract mucosa is due to antigenic peptides with Mr identical to PIP. While the presence of PIP in the ileum is compatible with a function as an enterooxyntin, it is not possible at present to explain the physiologic role of PIP entirely as a hormone regulating acid secretion in light of the immunohistochemical distribution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47406/1/418_2004_Article_BF00492352.pd

Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics

Aberrant crypt foci (ACF) have been identified on the colonic mucosal surface of rodents treated with colon carcinogens and of humans after methylene-blue staining and observation under a light microscope. Several lines of evidence strongly suggest that ACF with certain morphological, histological, cell kinetics, and genetic features are precursor lesions of colon cancer both in rodents and in humans. Thus, ACF represent the earliest step in colorectal carcinogenesis. This paper has the main purpose of reviewing the evidence supporting this view, with particular emphasis on cell and crypt dynamics in ACF. ACF have been used as intermediate biomarkers of cancer development in animal studies aimed at the identification of colon carcinogens and chemopreventive agents. Recently, evidence has also shown that ACF can be effectively employed in chemopreventive studies also in humans