Expression of Mismatch Repair Genes, HMLH1, HMSH2 and HMSH6 in 195 Small Intestinal Adenocarcinomas
WJ Sung, YK Bae, S-M Hong, The Korean Small Intestinal Cancer Study Group. Yeungnam University College of Medicine, Daegu, Korea; Johns Hopkins Medical Institutions, Baltimore, MD
Background: Primary adenocarcinomas of the small intestine are uncommon. Although much has been reported about microsatellite instability related to colorectal adenocarcinomas, little is known about the role of mismatch repair genes involved in small intestinal adenocarcinoma (SIAC).
Design: A total of 195 SIAC cases were collected from 22 institutions in Korea and tissue microarrays were made. Immunohistochemistry was performed using monoclonal antibodies for hMLH1, hMSH2 and hMSH6.
Results: One hundred twenty two male and 73 female patients with median age of 59 years old (range 23-86) presented with SIACs located at the duodenum (106), jejunum (59) and ileum (30). The histologic type consisted of 177 adenocarcinomas, 9 mucinous carcinomas, 4 signet ring cell carcinomas and 5 undifferented carcinomas. Immunohistochemistry revealed loss of expression for hMLH1, hMSH2 and hMSH6 in 25/193 (13%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMLH1 expression was more frequent in female, while loss of hMSH2 expression was more frequent in male (p=0.05). The loss of hMLH1 expression was associated with depth of invasion (pT) (p=0.038) and expression of hMSH2 and hMSH6 was correlated with histologic type (mucinous and undifferented carcinoma > adenocarcinoma, p<0.001 and p=0.019, respectively) All patients with peritumoral adenoma expressed hMSH6 expression, while 29 of 166 patients without peritumoral adenoma showed loss of hMSH6 expression (p=0.015).
Conclusions: The expression of mismatch repair genes in SIACs is associated with depth of invasion, histologic type and the presence of peritumoral adenoma. And the frequencies of aberrant expression of mismatch repair genes in SIACs are similar to those of colorectal adenocarcinomas. Our results suggest that small intestinal carcinogenesis is similar to that of colorectal carcinoma.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 70, Tuesday Afternoon