50 例免疫组织化学检测错配修复（MMR）缺陷型子宫内膜癌的临床病理特征：印度单机构可行性研究。

Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India.

机构信息

Department of Surgical Pathology, Tata Memorial Hospital, HBNI University, Mumbai, India.

出版信息

Ann Diagn Pathol. 2020 Aug;47:151558. doi: 10.1016/j.anndiagpath.2020.151558. Epub 2020 Jun 20.

DOI:10.1016/j.anndiagpath.2020.151558

PMID:32619922

Abstract

There are few comprehensive studies from Asia on clinicopathologic features of mismatch repair (MMR)-deficient endometrial carcinomas, including rarely from our country. One hundred and four cases of endometrial carcinomas were tested for four MMR proteins by immunohistochemistry. Among 50 MMR-deficient (MMRd) tumors(48%), age-range was 27-68 years(median = 53) and tumor size(n = 34) varied from 1.2-10 cm(average = 4.6). Lower uterine segment(LUS) was involved in 21/31 cases(67.7%). Histopathologically, all cases were endometrioid adenocarcinomas(EMACs), of FIGO grade 2(low-grade)(18 cases) and 3(high-grade)(32 cases), displaying de-differentiated, undifferentiated and lymphoepithelioma(LE)-like patterns, in 24 cases(48%). Tumor infiltration ≥ half of myometrium was seen in 30/44 cases (68.1%); lymphovascular emboli in 19/43 cases(44.1%); and lymph node metastasis in 7/22(31.8%) cases. Uncommonly, clear cell component(n = 2) and focal neuroendocrine differentiation (n = 2) were observed. Immunohistochemically, tumor cells showed paired loss of MLH1 and PMS2 in 33(66%) and MSH2 and MSH6 in 14(28%) cases, along with loss of MSH2 and PMS2, in two and a single case, respectively. Nine patients(18%) were treated for another cancer and 9/33(27.2%) disclosed familial history of cancer. MSH2 was the most frequently lost MMR protein in those cases. Additionally, tumor cells displayed ER positivity in 41/50 cases(82%), PR in 38/41cases(92.6%) and wild-type p53 staining in 24/28 cases(85.7%). Tumor with LE-pattern showed PDLI immunoexpression. Certain clinicopathologic features suggestive for MMRd associated ECs, such as relatively large-sized tumors, involving LUS; especially high-grade, infiltrative EMACs, with undifferentiated/de-differentiated, and LE-like patterns; showing deep muscle invasion, frequent PR immunoexpression and invariably, wild-type p53 immunostaining can be useful in screening cases of Lynch syndrome. This constitutes the first report on these tumors from our country.

摘要

有很少来自亚洲的关于错配修复（MMR）缺陷型子宫内膜癌的临床病理特征的综合研究，包括来自我们国家的研究。通过免疫组织化学方法对 104 例子宫内膜癌患者的 4 种 MMR 蛋白进行了检测。在 50 例 MMR 缺陷（MMRd）肿瘤（48%）中，年龄范围为 27-68 岁（中位数=53），肿瘤大小（n=34）为 1.2-10cm（平均=4.6）。21/31 例（67.7%）累及下段子宫。组织病理学上，所有病例均为子宫内膜样腺癌（EMAC），FIGO 分级 2（低级别）（18 例）和 3（高级别）（32 例），有 24 例（48%）表现出去分化、未分化和淋巴上皮样（LE）样形态。30/44 例（68.1%）肿瘤浸润超过一半的子宫肌层；19/43 例（44.1%）有血管淋巴管浸润；22 例中有 7 例（31.8%）淋巴结转移。罕见的是，观察到 2 例透明细胞成分和 2 例局灶神经内分泌分化。免疫组织化学染色显示，33 例（66%）肿瘤细胞显示 MLH1 和 PMS2 配对丢失，14 例（28%）显示 MSH2 和 MSH6 丢失，2 例和 1 例分别丢失 MSH2 和 PMS2。9 例（18%）患者因其他癌症接受治疗，9/33 例（27.2%）患者有癌症家族史。在这些病例中，MSH2 是最常丢失的 MMR 蛋白。此外，50 例中有 41 例（82%）肿瘤细胞显示 ER 阳性，38 例中有 38 例（92.6%）显示 PR 阳性，28 例中有 24 例（85.7%）显示野生型 p53 染色阳性。具有 LE 样形态的肿瘤显示 PDLI 免疫表达。一些提示 MMRd 相关 ECs 的临床病理特征，如相对较大的肿瘤大小，累及下段子宫；特别是高级别、浸润性的 EMACs，有未分化/去分化和 LE 样形态；表现为深部肌层浸润、PR 免疫表达频繁，以及不变的野生型 p53 免疫染色，有助于筛选林奇综合征病例。这是来自我们国家的此类肿瘤的首次报道。