[Molecular etiology of colorectal carcinogenesis, clinical manifestations and therapy].

Mutations of tumor suppressor genes, of the mismatch DNA repair system, and of the TGF-beta-II-receptor are the main causes for a higher risk of colorectal cancer. Among mutations of the Ape gene, which characterize the clinical manifestation of the familial polyposis (FAP), point mutations are dominating which create new stop codons or arise from deletions or insertions of nucleotides causing frame shifts. Because the binding site of beta-catenin is localized in the C-terminus of the Ape protein, disturbances result in the cellular signal transfer from its loss.

Significance of apoptosis in the process of tumorigenesis in colorectal mucosa and adenomas in FAP patients.

The relation between proliferation and apoptosis was studied in colorectal mucosal biopsies (N = 41), tubular adenomas (TA) (N = 104) and tubulovillous adenomas (TVA) (N = 34) from 37 FAP patients. Proliferative activity was determined by cell cycle distribution analysis. In addition, transcriptional capacity was determined by chromatin in situ testing.

Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer.

The clinical course of familial adenomatous polyposis (FAP) varies considerably between patients. Prediction of the severity of the disease is important in the interest of effective cancer prevention. We examined whether age at diagnosis of FAP due to gastrointestinal symptoms and age at death due to colorectal cancer are related to the site of mutation in the responsible gene.

[Autoradiography of DNA synthesis in colonic mucosa of patients with familial adenomatosis coli].

In connection with routine endoscopic examinations of 31 patients with familial adenomatosis coli and 28 health kindreds of patients with familial adenomatosis coli we investigated by autoradiography the in vitro incorporation of 3H-thymidine into bioptic mucosal particles from colon and adenomas. Within the 5-year follow-up period there was found a significantly increased labelling index of polyps and the surrounding mucosa in patients with polyposis independing on the time elapsed after operation. In 12 of 28 kindreds the histological normal colonic mucosa showed an increased labelling index too.