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Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer

2017; Impact Journals LLC; Volume: 9; Issue: 5 Linguagem: Inglês

10.18632/oncotarget.23790

1949-2553

Hitomi Yamashita, Kentaro Nakayama, Masako Ishikawa, Kohei Nakamura, Tomoka Ishibashi, Kaori Sanuki, Ruriko Ono, Hiroki Sasamori, Toshiko Minamoto, Kouji Iida, Razia Sultana, Noriyoshi Ishikawa, Satoru Kyo,

Cancer Genomics and Diagnostics

// Hitomi Yamashita 1 , Kentaro Nakayama 1 , Masako Ishikawa 1 , Kohei Nakamura 1 , Tomoka Ishibashi 1 , Kaori Sanuki 1 , Ruriko Ono 1 , Hiroki Sasamori 1 , Toshiko Minamoto 1 , Kouji Iida 1 , Razia Sultana 1 , Noriyoshi Ishikawa 2 and Satoru Kyo 1 1 Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan 2 Department of Organ Pathology, Shimane University School of Medicine, Izumo, Japan Correspondence to: Kentaro Nakayama, email: // Keywords : microsatellite instability; endometrial cancer; immune checkpoint inhibitor; immunohistochemistry; mismatch repair protein; Immunology Received : September 07, 2017 Accepted : October 28, 2017 Published : December 31, 2017 Abstract In recent years, it has become evident that tumor cells have immune escape mechanisms, and immune checkpoint inhibitor therapy (anti-PD-1/PD-L1 antibody) has shown benefit in various cancers. In endometrial tumors with microsatellite-instability (MSI), somatic mutations have the potential to encode ‘’non-self’’ immunogenic antigens, and lymphocytes have been shown to infiltrate the tumor. Therefore, immune checkpoint inhibitor therapy might be effective in endometrial cancers with MSI. Expression of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), the presence of tumor-infiltrating lymphocytes (CD8+), and PD-1/PD-L1 expression were assessed by immunohistochemistry in 149 patients with endometrial cancer. We examined whether tumors with MSI had an enhanced immune microenvironment and whether MSI could be a predictor of the therapeutic effect of PD-1/PD-L1 immunotherapy in endometrial cancer. Loss of MMR protein expression was identified in 42 (28.2%) of 149 patients (MSI group) with endometrial cancer. There was no significant relationship between MSI status and age ( p = 0.193), histological grade ( p = 0.097), FIGO stage ( p = 0.508), pelvic lymph node metastasis ( p = 0.139), or depth of myometrial invasion ( p = 0.494). However, the presence of tumor-infiltrating lymphocytes (CD8+) and PD-L1/PD-1 expression were significantly higher in the MSI group compared to the microsatellite-stable group ( p = 0.002, p = 0.001, and p = 0.008, respectively). These results suggest that immune checkpoint inhibitors (anti-PD-1/PD-L1 antibody) could be effective in endometrial cancers with MSI. The presence of MSI may be a biomarker for good response to PD-1/PD-L1 immunotherapy in endometrial cancer.