Usefulness of immunohistochemistry for mismatch repair protein and microsatellite instability examination in adenocarcinoma and background endometrium of sporadic endometrial cancer cases

• Published in: The journal of obstetrics and gynaecology research Vol. 45; no. 10; pp. 2037 - 2042
• Main Authors: Saeki, Harumi, Hlaing, May T., Horimoto, Yoshiya, Kajino, Kazunori, Ohtsuji, Naomi, Fujino, Kazunari, Terao, Yasuhisa, Hino, Okio
• Format: Journal Article
• Language: English
• Published: Kyoto, Japan John Wiley & Sons Australia, Ltd 01.10.2019; Wiley Subscription Services, Inc
• Subjects: Adenocarcinoma; Adenocarcinoma - enzymology; Adenocarcinoma - genetics; Colorectal cancer; DNA Mismatch Repair; DNA repair; DNA Repair Enzymes - metabolism; Endometrial cancer; endometrial hyperplasia; Endometrial Neoplasms - enzymology; Endometrial Neoplasms - genetics; Endometrium; Endometrium - enzymology; Female; Genetic disorders; Humans; Hyperplasia; Immunohistochemistry; Lynch syndrome; Menopause; Microsatellite Instability; Middle Aged; Mismatch repair; mismatch repair gene; MLH1 protein; MMR protein; Proteins; Tumorigenesis; endometrial cancer; microsatellite instability; endometrial hyperplasia; Lynch syndrome; mismatch repair gene
• ISSN: 1341-8076; 1447-0756
• DOI: 10.1111/jog.14061

Aim Microsatellite instability (MSI), which reflects loss of DNA mismatch repair (MMR) activity, and immunohistochemistry (IHC) for MMR proteins are employed as screening examinations for Lynch syndrome (LS). Recent studies revealed that there is a population of MSI‐high tumors in sporadic endometrial cancer (EC). However, MSI data for Japanese EC patients are scarce. Furthermore, sporadic estrogen‐dependent EC (type I) is generally considered to arise from hyperplasia. Because LS is usually associated with type I EC, we hypothesized that MSI might be involved in the oncogenic process in some sporadic EC. We conducted MSI testing to reveal MSI status in sporadic Japanese EC. IHC for MMR proteins was also performed. Methods Ninety‐eight tissue samples of sporadic ECs from Japanese patients were used for IHC and MSI examinations. We also evaluated MMR protein expressions in the background normal endometrium. Results Microsatellite instability‐high was observed in 10.2% of 98 cases with sporadic EC, a lower percentage than that in Western studies. Loss of some MMR proteins was observed in 23 cases (23.5%) and there was a significant correlation with MSI‐high status (P < 0.001). Concerning the background endometrium, two cases showed partial loss of MLH1 and PMS2, corresponding to adjacent EC lesions, suggesting that MMR deficiency may already be present in the background endometrium. Conclusion The MSI‐high rate was low in our Japanese cohort. Our data confirmed the usefulness of MMR protein assessment for MSI screening in Japanese EC patients. Furthermore, IHC of the background endometrium might reveal the mechanism of MSI‐high tumorigenesis.