Prognostic value of hMLH1 methylation and microsatellite instability in pancreatic endocrine neoplasms☆
Section snippets
Patients and tissues
Forty-eight patients who underwent resection of a PEN at The Johns Hopkins Hospital between 1991 and 2001 were studied. After permission from the Johns Hopkins University institutional review board, tissue specimens were collected retrospectively as formalin-fixed, paraffin-embedded blocks from the Department of Pathology. Information regarding tumor classification (pathologic grade, size, and stage), patient characteristics (age and gender), and clinical follow-up data was ascertained through
hMLH1 hypermethylation
Similar to our previous report that examined the importance of aberrant promoter methylation of multiple tumor suppressor genes in islet cell tumors,17 we discovered hMLH1 hypermethylation in 23% of all PENs. However, we did not find promoter methylation within the tumor-free tissue margins that were adjacent to the primary neoplasms (Fig 1). Despite careful microdissection of the tumor sections, the presence of unmethylated alleles within the hMLH1-methylated tumors likely reflects the
Discussion
Strict criteria for the determination of MSI in neoplasms that arise from the exocrine or endocrine pancreas remain unestablished. Although some studies have questioned whether microsatellite variability that is associated with less than 40% of studied markers truly reflects defective DNA mismatch repair, we classified neoplasms as MSI-positive if size variation was found for the BAT26 marker or any 2 microsatellite loci.19., 20. Overall, MSI was discovered in 5 of the 48 PENs (10%), and each
Acknowledgements
We thank Kornel Schuebel, PhD, for his expert advice about the study of MSI in human neoplasms.
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Presented at the 24th Annual Meeting of the American Association of Endocrine Surgeons, San Diego, California, May 1l-14, 2003.
Supported in part by grants from the Stavros S. Niarchos Foundation and National Cancer Institute grant CA-84986 of the Early Detection Research Network.