Abstract
Several morphologic features have been reported to be predictive of abnormal expression of mismatch repair (MMR) proteins in endometrial and colon carcinomas. Although it is known that abnormal MMR expression is increased in frequency in ovarian endometrioid and clear cell carcinomas, no such histologic correlation has been identified. We reviewed 109 unselected ovarian clear cell carcinomas for specific tumor characteristics (architecture, nuclear atypia, signet ring cells, stromal hyalinization, background precursor) and inflammatory response (peritumoral lymphocytes found along the leading edge of the tumor, intratumoral stromal inflammation found within the tumor, percentage of plasma cells in the intratumoral stromal inflammation, tumor-infiltrating lymphocytes) and performed immunohistochemistry for all 4 MMR proteins. Abnormal MMR expression was identified in 6% of tumors and included MSH2/MSH6 (3), MLH1/PMS2 (1), MSH6 (1), and PMS2 (1). These patients had a mean age of 40 (range, 31 to 48) years, which contrasted with a mean of 53.2 (range, 28 to 82) years for the overall cohort. One had a concurrent diagnosis of endometrial carcinoma, whereas another had a family history of endometrial carcinoma. None had a personal/family history of colonic carcinoma. Tumors with diffuse intratumoral stromal inflammation and peritumoral lymphocytes were more frequently associated with MMR loss on univariate analysis (P<0.001 and 0.047, respectively) with diffuse intratumoral stromal inflammation remaining a significant independent predictor on multivariate analysis. None of the other morphologic features evaluated reached statistical significance. Although previous series have been unable to identify a relationship between histology and MMR expression, this study identified a correlation with diffuse intratumoral stromal inflammation and peritumoral lymphocytes, 2 features that potentially could be selected for MMR analysis if corroborated by other studies.
摘要
据报道,子宫内膜癌和结肠癌中几种形态学特征可提示出现错配修复(MMR)蛋白的异常表达。虽然已知卵巢子宫内膜样癌和透明细胞癌中MMR表达异常的比例增加,但还未发现与组织学有相关性。我们复习了109例未经选择的卵巢透明细胞癌,分析其特异性肿瘤特征(结构,核非典型性,印戒样细胞,间质透明样变,背景中前驱病变)和炎症反应(肿瘤前缘肿瘤周围淋巴细胞,肿瘤内间质炎症,肿瘤内间质炎症中浆细胞百分比,肿瘤中浸润的淋巴细胞)和所有4种MMR蛋白免疫组化。
6%的肿瘤发现MMR表达异常,包括MSH2/MSH6 (3),MLH1/PMS2 (1),MSH6 (1)和PMS2 (1)。这些患者平均年龄40(31-48)岁,而全部肿瘤患者的平均年龄为53.2(28-82)岁。一例合并子宫内膜癌,而另一例有子宫内膜癌家族史。均无结肠癌个人/家族史。单变量分析表明伴弥漫肿瘤内间质炎症和肿瘤周淋巴细胞的肿瘤与MMR丢失密切相关(分别为P<0.001和 0.047),多变量分析表明弥漫性肿瘤内间质炎症还是显著独立预后因子。上述其他形态学特征均无统计学意义。
虽然先前的研究没有发现组织学和MMR表达之间的关系,但本研究发现弥漫性肿瘤内间质炎症和肿瘤周围淋巴细胞与MMR表达有关,如果被其他研究确认,那这2个特征可作为MMR分析的筛选指征。
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