Rambau Peter F, Duggan Máire A, Ghatage Prafull, Warfa Khadija, Steed Helen, Perrier Renee, Kelemen Linda E, Köbel Martin
Department of Pathology, Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania.
Department of Pathology and Laboratory Medicine, Calgary Laboratory Services/Alberta Health Services and University of Calgary, Calgary, AB, Canada.
Histopathology. 2016 Aug;69(2):288-97. doi: 10.1111/his.12934. Epub 2016 Feb 26.
Lynch syndrome screening in ovarian carcinoma is controversial. The aim of this study was to assess the frequency of deficient mismatch repair (dMMR) protein in a retrospective cohort enriched for non-high-grade serous carcinomas and its association with outcome within histological types.
Tissue microarrays representing 612 ovarian carcinomas were tested for mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry. dMMR was detected in 13.8% of endometrioid and 2.4% of clear cell carcinomas, but not in other histological types. Within endometrioid carcinomas, 11 of 25 dMMR cases showed abnormal MLH1/PMS2, 10 cases showed abnormal MSH2/MSH6, and four cases showed only abnormal MSH6, indicating that at least 7.7% of endometrioid carcinomas have dMMR probably related to Lynch syndrome. The four dMMR clear cell carcinomas showed abnormal MSH2/MSH6 in three cases and only abnormal MSH6 in one case, all probably related to Lynch syndrome. Within endometrioid carcinomas, dMMR was significantly associated with age <50 years, synchronous endometrial endometrioid carcinoma, a higher CA125 level at diagnosis, higher FIGO grade, absence of ARID1A, and at least 20 CD8-positive intraepithelial lymphocytes per high-power field, but was not associated with cancer-specific death. Age <50 years, higher CA125 levels at diagnosis and at least 20 CD8-positive intraepithelial lymphocytes per high-power field remained significant after adjustment for multiple testing, but their sensitivity for identifying dMMR remained insufficient.
Our data support the policy of histotype-specific Lynch syndrome screening in ovarian carcinoma confined to endometrioid and clear cell carcinomas.
卵巢癌中林奇综合征的筛查存在争议。本研究的目的是评估在一个以非高级别浆液性癌为主的回顾性队列中错配修复缺陷（dMMR）蛋白的频率及其与组织学类型内预后的关联。
通过免疫组织化学检测了代表612例卵巢癌的组织芯片中的错配修复蛋白（MLH1、PMS2、MSH2和MSH6）。在13.8%的子宫内膜样癌和2.4%的透明细胞癌中检测到dMMR，但在其他组织学类型中未检测到。在子宫内膜样癌中，25例dMMR病例中有11例显示MLH1/PMS2异常，10例显示MSH2/MSH6异常，4例仅显示MSH6异常，表明至少7.7%的子宫内膜样癌存在可能与林奇综合征相关的dMMR。4例dMMR透明细胞癌中，3例显示MSH2/MSH6异常，1例仅显示MSH6异常，均可能与林奇综合征相关。在子宫内膜样癌中，dMMR与年龄<50岁、同步性子宫内膜样癌、诊断时较高的CA125水平、较高的国际妇产科联盟（FIGO）分级、ARID1A缺失以及每高倍视野至少20个CD8阳性上皮内淋巴细胞显著相关，但与癌症特异性死亡无关。在进行多重检验校正后，年龄<50岁、诊断时较高的CA125水平以及每高倍视野至少20个CD8阳性上皮内淋巴细胞仍然具有显著性，但它们识别dMMR的敏感性仍然不足。
我们的数据支持在卵巢癌中仅限于子宫内膜样癌和透明细胞癌进行组织学类型特异性林奇综合征筛查的策略。
