Prevalence and clinicopathologic features of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome in Chinese American patients in south Brooklyn, New York.

Abstract

441 Background: HNPCC is a hereditary disorder that predisposes to colorectal and other cancers before 50 years old and in multiple generations, with a prevalence of 2 to 5% in Caucasians. It is associated with mutations in DNA mismatch repair genes (MMR). The gold standard for diagnosis is genomic DNA sequencing. Immunohistochemical staining (IHC) is sensitive to predict but not diagnostic for HNPCC, as acquired hypermethylation of MLH1 promoter can present with negative IHC staining. We aimed to study the prevalence and clinicopathological features of HNPCC in Asian patients. Methods: IHC for 4 MMR protein expressions on tumor specimens, commercial MLH1 methylation studies and genomic sequencings were performed on eligible and selected patients diagnosed of colon, gastric or endometrial cancers. Results: 117 patients were identified (2000 to 2012), 55 M and 62 F, ranges from 23 to 92 years old. Seven cases of MMR deficiency were found: 5 with colon cancer (81 patients), 2 with gastric cancer (31 patients) and 0 with endometrial cancer (5 patients). Among the 81 colon cancer patients, 20 had cancer younger than 50 years old; and among them, 3 cases of MMR deficiency were confirmed by DNA sequencing. One patient was found to have a unique previously unreported suspected deleterious mutation. The other 2 patients had MLH1 promoter hypermethylation indicating acquired abnormality. 31 patients had gastric cancer, and 2 cases of MMR deficiency were found, including 1 MLH1 promoter hypermethylation and another isolated PMS2 deficiency by IHC. Conclusions: The prevalence of HNPCC in Chinese colon cancer patients in South Brooklyn is 3.7% (3/81). All cases were found in patients younger than 50 years old with a prevalence of 15% (3/20). Hypermethylation in MLH1 can be seen in both colon and gastric cancers. The screening in Chinese Americans for HNPCC is as important as in Caucasian population, and should be done also in Asian gastric cancer patients as well.