Garg Karuna, Leitao Mario M, Kauff Noah D, Hansen Jessica, Kosarin Kristi, Shia Jinru, Soslow Robert A
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Am J Surg Pathol. 2009 Jun;33(6):925-33. doi: 10.1097/PAS.0b013e318197a046.
Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a high risk for endometrial cancer (EC) and frequently present with a gynecologic cancer as their first or sentinel malignancy. Identification of these patients is important given their personal and family risk for synchronous and metachronous tumors. The revised Bethesda Guidelines provide screening criteria for HNPCC in colorectal cancers. However, there are currently no such screening recommendations for women with endometrial carcinoma. We applied some of the colorectal cancer screening criteria, including age and tumor morphology, to endometrial endometrioid carcinoma. The purpose of this study was to describe patient and tumor characteristics and to assess the ability of these criteria to enhance detection of mismatch repair (MMR) deficiency, and hence HNPCC in EC. Immunohistochemistry (IHC) for DNA mismatch repair (IHC-MMR) proteins was performed in a defined subset of patients with EC. This included women younger than 50 years of age and women >or=50 years whose tumors showed morphologic features suggestive of MMR deficiency (TM-MMR). The extent of IHC-MMR in the older patient group was compared with that in a comparison group of EC >or=50 years that was previously analyzed for microsatellite instability status. Seventy-one patients met the selection criteria for IHC testing; 32 (45%) showed abnormal results. The rate of IHC abnormality in the younger group was approximately 30% with a nearly equal distribution of MLH1/PMS2 and MSH2/MSH6 abnormalities. In the older age group, TM-MMR triggered IHC analysis in 31 of 34 cases. Of these, 18 cases showed loss of IHC-MMR (58% of cases), 7 with loss of MSH2/MSH6. In contrast, the rate of microsatellite instability in the comparison group was only 21%. The IHC abnormal group showed more frequent tumor infiltrating lymphocytes, dedifferentiated EC, more tumors centered in the lower uterine segment, and more frequent synchronous clear cell carcinomas of the ovary than tumors with a normal immunophenotype. Although many of the patients with loss of IHC-MMR showed personal and/or family history (13 of 32) of HNPCC-associated tumors, most did not. Tumor morphology (TM-MMR) along with IHC-MMR enhances the detection of EC patients at risk of HNPCC.
遗传性非息肉病性结直肠癌（HNPCC）女性患子宫内膜癌（EC）的风险很高，并且常以妇科癌症作为其首发或哨兵恶性肿瘤。鉴于这些患者发生同步和异时性肿瘤的个人及家族风险，识别出这些患者很重要。修订后的贝塞斯达指南为结直肠癌中的HNPCC提供了筛查标准。然而，目前对于子宫内膜癌女性尚无此类筛查建议。我们将一些结直肠癌筛查标准，包括年龄和肿瘤形态，应用于子宫内膜样腺癌。本研究的目的是描述患者和肿瘤特征，并评估这些标准增强错配修复（MMR）缺陷检测的能力，从而在子宫内膜癌中检测出HNPCC。对特定子集的子宫内膜癌患者进行了DNA错配修复蛋白的免疫组织化学（IHC）检测（免疫组化MMR）。这包括年龄小于50岁的女性以及年龄大于或等于50岁且肿瘤显示出提示MMR缺陷形态特征（TM-MMR）的女性。将老年患者组中免疫组化MMR的程度与先前分析过微卫星不稳定性状态的年龄大于或等于50岁的子宫内膜癌对照组进行比较。71例患者符合免疫组化检测的选择标准；32例（45%）结果异常。较年轻组中免疫组化异常率约为30%，MLH1/PMS2和MSH2/MSH6异常分布几乎相等。在老年组中，34例中有31例因TM-MMR触发免疫组化分析。其中，18例显示免疫组化MMR缺失（占病例的58%），7例MSH2/MSH6缺失。相比之下，对照组中的微卫星不稳定性率仅为21%。与免疫表型正常的肿瘤相比，免疫组化异常组显示肿瘤浸润淋巴细胞更常见、子宫内膜样腺癌去分化、更多肿瘤位于子宫下段且卵巢同步透明细胞癌更常见。尽管许多免疫组化MMR缺失的患者有HNPCC相关肿瘤的个人和/或家族史（32例中有13例），但大多数没有。肿瘤形态（TM-MMR）与免疫组化MMR一起可增强对有HNPCC风险的子宫内膜癌患者的检测。
