Frequency of Mismatch Repair Deficiency/High Microsatellite Instability and Its Role as a Predictive Biomarker of Response to Immune Checkpoint Inhibitors in Gynecologic Cancers
| Autor: | Joseph J, Noh, Min Kyu, Kim, Min Chul, Choi, Jeong-Won, Lee, Hyun, Park, Sang Geun, Jung, Won Duk, Joo, Seung Hun, Song, Chan, Lee |
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| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
Brain Neoplasms Genital Neoplasms Female Uterine Cervical Neoplasms DNA Mismatch Repair Endometrial Neoplasms DNA-Binding Proteins MutS Homolog 2 Protein Oncology Neoplastic Syndromes Hereditary Uterine Neoplasms Humans Female Microsatellite Instability Neoplasm Recurrence Local Colorectal Neoplasms MutL Protein Homolog 1 Immune Checkpoint Inhibitors Biomarkers Mismatch Repair Endonuclease PMS2 |
| Zdroj: | Cancer Research and Treatment. 54:1200-1208 |
| ISSN: | 2005-9256 1598-2998 |
| DOI: | 10.4143/crt.2021.828 |
| Popis: | PurposeThis study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent gynecologic cancers according to MMR/MSI status.Materials and MethodsWe conducted a multi-center retrospective review on the patients who were diagnosed with gynecologic cancers between 2015 and 2020. Their clinicopathologic information, results of immunohistochemistry staining for MLH1/MSH2/MSH6/PMS2 and MSI analysis, tumor response to treatment with ICIs were investigated.ResultsAmong 1,093 patients included in the analysis, MMRd/MSI-H was most frequent in endometrial/uterine cancers (34.8%, 164/471), followed by ovarian, tubal, and peritoneal cancers (12.8%, 54/422) and cervical cancer (11.3%, 21/186). When assessed by histology without regard for cancer types, the frequency of MMRd/MSI-H was 11.0% (38/345) in high-grade serous adenocarcinoma, 38.6% (117/303) in endometrioid adenocarcinoma, and 30.2% (16/53) in carcinosarcoma. A total of 114 patients were treated with ICIs at least once. The objective response rate (ORR) was 21.6% (8/37) in cervical cancer, 4.7% (2/43) in ovarian cancer, and 25.8% (8/31) in endometrial/uterine cancers. Univariate regression analysis identified MMRd/MSI-H as the only significant factor associated with the ORR (28.9% [11/38] vs. 11.8% [9/76]; odds ratio, 3.033; 95% confidence interval, 1.129–8.144; p=0.028).ConclusionThe frequency of MMRd/MSI-H is moderate to high in gynecologic cancers in the Korean population. MMRd/MSI-H could be effective predictive biomarkers in gynecologic cancers of any type. |
| Databáze: | OpenAIRE |
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