Ovarian Endometrioid Adenocarcinoma: Incidence and Clinical Significance of the Morphologic and Immunohistochemical Markers of Mismatch Repair Protein Defects and Tumor Microsatellite Instability
Ovarian Endometrioid Adenocarcinoma: Incidence and Clinical Significance of the Morphologic and Immunohistochemical Markers of Mismatch Repair Protein Defects and Tumor Microsatellite Instability
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DOI：
10.1097/pas.0b013e31823bc434
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发表时间：
2012-02-01
影响因子：
5.6
通讯作者：
Rabban, Joseph T.
中科院分区：
文献类型：
--
作者：
Aysal, Anil;Karnezis, Anthony;Rabban, Joseph T.
一组子宫癌患者表现出缺陷错配修复蛋白(MMR)和微卫星不稳定(MSI)，可能患有林奇综合征，这也增加了患者和她的家人患结直肠癌和其他癌症的风险。基于临床和病理标准的筛查算法在确定哪些子宫癌患者最有可能受益于明确的林奇综合征基因测试方面是有效的。卵巢癌，特别是子宫内膜样腺癌，也与林奇综合征有关，尽管风险比子宫癌小得多。本研究评估了目前用于筛查子宫癌以进行进一步Lynch综合征检测的形态标准[肿瘤浸润性淋巴细胞(TILs)、瘤周淋巴细胞(PTLS)、去分化形态]是否适用于卵巢癌。在同一机构治疗的71例单纯卵巢子宫内膜样腺癌患者中，13%的患者有TIL，3%的患者有PTLS，没有去分化的形态。总体而言，10%的肿瘤具有异常的MMR蛋白状态，定义为MLH1、MSH2、MSH6和/或PMS2的免疫组织化学完全缺失。这些具有异常MMR状态的肿瘤中的每一个都使用基于聚合酶链式反应的检测方法显示MSI，评估5个单核苷酸重复标记。未发现患者年龄、TIL、PTLS或一系列其他形态变量与MMR蛋白状态/MSI之间的关系。仅1/7 MMR/MSI异常的肿瘤有TILs/PTLS。在14例死亡患者中，12例(86%)MMR状态正常。7例MMR/MSI异常的肿瘤患者中，5例(71%)无病存活。7例卵巢肿瘤MMR/MSI异常的患者中，5例合并子宫肿瘤。这项研究表明，用于筛查子宫癌患者进行进一步林奇综合征测试的形态标准不适用于卵巢癌患者。虽然MMR/MSI异常在这项研究中没有预后价值，但它确实预测了肿瘤侵犯子宫。因此，在接受保留子宫手术的卵巢子宫内膜样腺癌患者中，MMR/MSI异常应促使对子宫内膜肿瘤的进一步诊断评估。
A subset of women with uterine cancer exhibiting defective mismatch repair (MMR) proteins and microsatellite instability (MSI) may have Lynch syndrome, which also confers a risk for colorectal cancer and other cancers in the patient and in her family. Screening algorithms based on clinical and pathologic criteria are effective in determining which patients with uterine cancer are most likely to benefit from definitive genetic testing for Lynch syndrome. Ovarian cancer, particularly endometrioid adenocarcinoma, is also associated with Lynch syndrome, although the risk is much smaller than for uterine cancer. This study evaluated whether the morphologic criteria [tumor-infiltrating lymphocytes (TILs), peritumoral lymphocytes (PTLs), dedifferentiated morphology)] currently used to screen uterine cancer for further Lynch syndrome testing can be applied to ovarian cancer. Among 71 patients with pure ovarian endometrioid adenocarcinoma treated at a single institution, 13% had a tumor with TILs, 3% had PTLs, and none had dedifferentiated morphology. Overall, 10% of tumors had abnormal MMR protein status, defined as complete immunohistochemical loss of expression of MLH1, MSH2, MSH6, and/or PMS2. Each of these tumors with abnormal MMR status demonstrated MSI using a polymerase chain reaction-based assay evaluating 5 mononucleotide repeat markers. No relationship was found between patient age, TILs, PTLs, or a spectrum of other morphologic variables and MMR protein status/MSI. Only 1/7 tumors with abnormal MMR/MSI had TILs/PTLs. Among 14 patients who died, 12 (86%) had normal MMR status. Among 7 patients with tumors with abnormal MMR/MSI, 5 (71%) were alive without disease. Concurrent uterine tumor was present in 5/7 patients whose ovarian tumor had abnormal MMR/MSI. This study suggests that the morphologic criteria used to screen patients with uterine cancer for further Lynch syndrome testing are not applicable in patients with ovarian cancer. Although abnormal MMR/MSI did not carry prognostic value in this study, it did predict the involvement of the uterus by the tumor. Thus, in patients with ovarian endometrioid adenocarcinoma who undergo uterus-sparing surgery, abnormal MMR/MSI should prompt further diagnostic evaluation of the endometrium for tumor.