Hereditary Non-polyposis Colorectal Cancer/Lynch Syndrome in Korean Patients with Endometrial Cancer

Center for Uterine Cancer, Research Institute and Hospital, National Cancer Center, 323, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, South Korea.
Japanese Journal of Clinical Oncology (Impact Factor: 2.02). 10/2010; 40(12):1121-7. DOI: 10.1093/jjco/hyq144
Source: PubMed


We investigate the frequency of hereditary non-polyposis colorectal cancer among Korean endometrial cancer patients according to two clinical criteria and the uptake rate of a genetic test and genetic status of such patients in routine clinical practice.
This was a retrospective study involving 161 consecutive endometrial cancer patients. Patients were classified into clinical and suspected hereditary non-polyposis colorectal cancer. Using direct sequencing, germline mutations were analyzed in the MLH1 and MSH2 genes.
There were four (2.5%) clinical hereditary non-polyposis colorectal cancer patients, three of whom underwent genetic testing, and a mutation (c.882delT) in the MSH2 gene was identified in one patient. There were also 14 (8.7%) suspected hereditary non-polyposis colorectal cancer patients, 6 of whom underwent genetic testing; 1 [1/6 (16.7%)] patient had a mutation (c.1757_1758insC) in the MLH1 gene and 1 patient had a sequence variant of unknown significance (c.1886A < G) in the MSH2 gene. Half of the patients (9 of 18) who met clinical or suspected hereditary non-polyposis colorectal cancer criteria declined genetic testing mainly for the reason of financial factor (8 of 9).
The proportion of hereditary non-polyposis colorectal cancer [11.2% (18 of 161)] was significant to offer genetic counseling and genetic testing in Korean endometrial cancer patients. Optimal financial support is crucial to increase the uptake rate of a genetic test.

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    • "LS has an incidence of 1:2000 – 1:660 [6]. LS is an autosomal dominant disorder caused by defective DNA mismatch repair genes (MLH1, MSH2, MSH6 or PMS2) [7,8]. About 2% of uterine cancer is attributable to LS and among affected women aged younger than 50 years the prevalence of LS increases to 9% [9]. "
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    • "Risk reducing surgery, based on genetic tests and genetic counseling for the hereditary portion of endometrial and ovarian cancer, might reduce their incidence. In Korean females, the hereditary portion of endometrial and ovarian cancer is significant, as is the case in other ethnic populations [1,2]. "
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    • "Frequency of Lynch syndrome in Korean endometrial cancer patients has been reported to be 3.5% (4/113) [14] and 11.2% (18/161) [15], but there are no reports describing synchronous gynecologic tumors. Therefore, we undertook the present study to evaluate the frequency of Lynch syndrome in Korean women with synchronous gynecologic tumors including endometrial and ovarian cancers based on family history and IHC. "
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    ABSTRACT: Lynch syndrome is a hereditary cancer syndrome that increases the risks of colorectal and gynecologic malignancies such as endometrial and ovarian cancer. Studies have shown that mutations in mismatch repair genes (MSH2, MSH6, and MLH1) are associated with Lynch syndrome. The aim of our study was to estimate the value of MSH2, MSH6, and MLH1 immunohistochemistry based on family history in a Korean sample. Thirty six women with synchronous gynecologic tumors of endometrial and ovarian cancer were identified among patients being treated at our institution. Among them, 32 patients had tumor blocks (total 62 slides) available for analysis. According to a diagnostic algorithm, we performed immunohistochemistry analyses. Staining was scored based on intensity and proportion (negative or 0: intensity undetectable or minimal, proportion <5%; weak or 1+: intensity mild, proportion 5-30%; strong or 2+: intensity moderate to marked, proportion 30-99%). Among 32 eligible patients, 9 (28%) had a family history of cancer. Six patients (19%) were negative for MLH1; among them, four (4/6) were negative at both sites. Nine patients (28%) were negative for MSH2 or MSH6 at both sites or negative for both MSH2 and MSH6. Among these three patients showed negative staining for both sites. The three patients showing negative staining for MLH1, MSH2, and MSH6 at both sites with family history were considered to be the screening positive groups of Lynch syndrome. In this study, the frequency of Lynch syndrome associated immunohistochemical staining (MLH1, MSH2, and MSH6) group was estimated as 9% (3/32) among Korean women with synchronous gynecologic tumors.
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