The predictive power of premalignant lesions of the stomach.

A Grace MRCPath, C. Gulmann MB, D.Butler MSc, M. Leader FRCPath, MD, E. Kay FRCPath, MD.

Department of Pathology, Royal College of Surgeons in Ireland, Dublin Ireland

While the overall incidence of gastric carcinoma is decreasing tumours of the proximal stomach appear to be on the increase. In addition pre neoplastic lesions (intestinal metaplasia) pose a considerable clinical problem in terms of follow up. Can we predict which cases will progress to invasive carcinoma? Aims: In an attempt to address some of the issues surrounding gastric carcinogenesis we evaluated a unique group of Irish and Chinese gastric resections. Materials & Methods: One hundred and fifty five gastric adenocarcinomas were retrieved from the files of China Medical University Shenyang, China and Beaumont Hospital Dublin. Immunohistochemistry was performed for CD44V6, p53 and adenomatous polyposis coli (APC) gene, APC was also evaluated by LOH. Telomerase was evaluated by in-situ hybridisation using digoxigenin labelling. Results: CD44V6 expression was detected more frequently in advanced gastric carcinomas and those with metastases, (47% AGC vs 30.5% EGC). P53 expression was not found to be of any value. APC expression by immunohistochemistry was absent in 78% of the tumours. This was also reflected at a DNA level by LOH. Telomerase expression was seen in 52.2% of this series of gastric carcinomas. In addition areas of intestinal metaplasia revealed CD44V6 expression, loss of APC and positive staining for telomerase. Conclusions: Successful interventional strategies for the early detection of gastric carcinoma and improved prognosis depends on the identification of reliably predictive molecular events. This study suggests that these three factors may be of value in early detection of gastric cancer and pre malignant changes such as intestinal metaplasia.

KEY WORDS: Premalignant, intestinal metaplasia, gastric carcinoma, telomerase.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Predictive Markers.