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DNA mismatch repair protein immunohistochemistry and MLH1 promotor methylation testing for practical molecular classification and the prediction of prognosis in endometrial cancer

 Jisup Kim  ;  Jin Kyoung Kong  ;  Wookyeom Yang  ;  Hanbyoul Cho  ;  Doo Byung Chay  ;  Bang Hyun Lee  ;  Seong Jin Cho  ;  Soonwon Hong  ;  Jae-Hoon Kim 
 CANCERS, Vol.10(9) : 279, 2018 
Journal Title
Issue Date
MLH1 promoter methylation test ; endometrial cancer ; mismatch repair deficiency ; molecular classification
The incidence of endometrial cancer is rapidly increasing worldwide, and its molecular classification has gained importance for new therapeutic approaches. This study sought to examine the clinicopathologic features and immune markers associated with the DNA mismatch repair (MMR) status and MLH1 promoter methylation status of endometrial cancer patients. A total of 173 patients with primary endometrial cancer who had received a hysterectomy were evaluated for four MMR proteins (MLH1, MSH2, MSH6, and PMS2), immune markers (CD8, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1)) and p53 by immunohistochemistry (IHC), followed by an MLH1 methylation test. Patients were classified into MMR deficiency or proficiency, sporadic cancer, or probable Lynch syndrome (PLS), and the clinicopathologic features (including the expression of peritumoral immune markers) and prognosis of each group were compared. Patients with MMR deficiency or PLS showed an increase in immune markers compared those with MMR proficiency or sporadic cancer, respectively, and PLS demonstrated higher immune marker expression than MLH1 promoter methylation. Regarding prognosis, patients with MMR deficiency showed significant adverse overall survival (OS) when in stages I and II. Practical molecular classifications based on p53 staining results, in addition to MMR or PLS status, revealed an increased predictive ability for OS compared with the European Society of Medical Oncologists (ESMO) risk groups. The results of this study suggest that PLS may be a better candidate for an immune checkpoint inhibitor than MMR deficiency. The practical molecular classification contributes not only to the screening of Lynch syndrome, but also assists in predicting the prognosis in endometrial cancer.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hoon(김재훈) ORCID logo https://orcid.org/0000-0001-6599-7065
Kim, Jisup(김지섭) ORCID logo https://orcid.org/0000-0002-0742-5517
Cho, Hanbyoul(조한별) ORCID logo https://orcid.org/0000-0002-6177-1648
Chay, Doo Byung(채두병) ORCID logo https://orcid.org/0000-0002-0648-4021
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
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