Telomerase activity and patient survival after surgery for gastric and oesophageal cancer

Objective The ribonucleoprotein telomerase extends telomeres in cancer cell s and has been proposed as a prognostic marker for cancer. We measured telo merase expression in proximal adenocarcinomas (those arising in the distal oesophagus or at the gastro-oesophageal junction) and distal adenocarcinoma s (those arising in the corpus or antrum of the stomach) of the foregut, an d correlated telomerase activity with pathological stage and post-operative survival. Design Surgical specimens were collected from patients undergoing resection s for gastric and oesophageal carcinomas. Haematoxylin and eosin histology provided data on the pathological tumour stage and pathological node stage. Methods The telomerase activity of cancer specimens was determined using th e telomeric repeat amplification protocol. A single pathologist, blinded to the results of the telomerase assays, reviewed all slides of cancers to as sign T and N stages. Results The cancers exhibited a wide range of telomerase expression. There was no significant difference between the telomerase activity of proximal a denocarcinomas (median, 551 U; 95% confidence interval, 154-2394 U; n = 26) and distal adenocarcinomas (median, 703 U; 95% confidence interval, 139-16 18 U; n = 20). Distal adenocarcinomas expressing high telomerase activity ( greater than the median) were significantly more advanced with regard to T stage than distal cancers expressing low telomerase levels (less than the m edian; P = 0.03, Mann-Whitney test). in distal adenocarcinomas, high telome rase activity was associated with poor patient survival (median 3 months) c ompared to low telomerase activity (median survival 22.4 months; P = 0.01, log-rank test). No such differences were observed for proximal adenocarcino mas. Conclusions There is a difference between gastric and oesophageal/gastro-oe sophageal junction adenocarcinomas in terms of the relationship with telome rase expression and clinico-pathological variables. Among patients with dis tal gastric adenocarcinoma, telomerase activity correlates with markers of advanced disease, whereas this relationship does not hold true in oesophage al/gastro-oesophageal junction adenocarcinomas. Telomerase activation may o ccur at different stages of the formation of the malignant phenotype in the se two cancers and may reflect differences in their pathogenesis. Telomeras e could be a prognostic marker in gastric but not in oesophageal adenocarci noma. Eur J Gastroenterol Hepatol 13:903-908 (C) 2001 Lippincott Williams & Wilkins.