Telomerase activity is frequently associated with neoplasia. It is a ribonucleoprotein capable of replacing telomeric DNA sequences that are lost at each cell division. Neoplastic progression in chronic ulcerative colitis is characterized by the development of epithelial dysplasia which is accompanied by genetic alterations. Therefore we tested telomerase activity in 128 biopsy samples of four colectomy specimens with long-standing ulcerative pancolitis by using the Telomerase PCR ELISA System. In three patients with multiple dysplastic or carcinomatous lesions, telomerase activity was detected in 22 samples with a regional association to dysplastic or carcinomatous areas. 15 of the samples with telomerase activity (68%) were found in dysplastic/carcinomatous samples or in the direct vicinity of dysplastic areas, 4 (18%), 2 positions (about 4 cm) and the remaining three (14%) not more than 3 positions away from such areas. In the fourth patient, resected because of clinical deterioration despite medical treatment and who had no dysplastic lesions, no telomerase activity was detected. These results show that telomerase activity might be used as a complementary marker to histology for the identification of patients with ulcerative colitis who are at an increased risk for neoplastic progression.

Biomarkers, Tumor↗

PubMedDate not supplied

Tumor-specific methylation patterns of erbB2 (HER2/neu) sequences in gastro-intestinal cancer.

To determine whether the sporadically occurring amplification of the oncogene erbB2/HER2 in gastrointestinal carcinomas is associated with additional changes of this sequence, DNA from 17 colorectal and 5 stomach carcinomas was analyzed for copy number, sequence rearrangement and DNA methylation by Southern blot hybridization. Amplification was detected in two cases. By applying the isochizomers Hpall and Mspl we tested for alterations in the DNA methylation status. Whereas in colon tumors with non-amplified erbB2 this status was unchanged, one case with erbB2 amplification showed additional MspI bands indicating a methylation of the amplified gene sequences. In stomach carcinoma, however, we detected differences between tumor and mucosa samples but not between amplified and non-amplified tumor samples. Independent of the DNA methylation status, significant amounts of the erbB2 oncoprotein were detected in the cases with gene amplification; weaker immunostaining of erbB2 was also seen in a few additional tumors.

Blotting, Southern↗