Department of Pathology, University of Chicago, 5841 S. Maryland Ave, Chicago, Illinois, USA.
Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, University of Chicago, 5841 S. Maryland Ave, Chicago, Illinois, USA.
Gynecol Oncol. 2018 Jun;149(3):570-574. doi: 10.1016/j.ygyno.2018.04.005. Epub 2018 Apr 13.
Universal screening of endometrial cancer (EC) for Lynch syndrome (LS) has been increasingly implemented in the past five to ten years. Most pathologists initiate screening with immunohistochemistry (IHC) for mismatch repair proteins (MMRPs), using either pre-surgical samplings (endometrial biopsy or curettage, EMB/C) or hysterectomy specimens. We report a systematic assessment of the equivalence of IHC for LS screening on EMB/C versus hysterectomy specimens.
We identified 99 patients diagnosed with endometrioid EC and performed IHC for MMRPs MLH1, MSH2, MSH6, and PMS2 on their diagnostic EMB/C and paired hysterectomy specimen. Each specimen was scored as MMRP-retained or MMRP-deficient.
Ninety-one EMB/Cs had carcinoma, while 8 EMB/Cs showed only complex atypical hyperplasia (CAH). Carcinoma was identified in all 99 hysterectomy specimens. Considering all 99 patients tested, concordance of MMRP expression pattern between EMB/C and paired hysterectomy specimen was 100%. Sixty-nine cases retained all four MMRPs, while 30 were MMRP deficient (26 MLH1- and PMS2-deficient, 3 MSH2- and MSH6-deficient, 1 PMS2-deficient).
In screening for LS in EC, IHC for MMRPs can be performed with identical accuracy on either EMB/C or hysterectomy specimens. Routine testing of diagnostic EMB/Cs may lead to earlier detection of MMRP deficiency, with improved patient uptake of genetic counseling and potential for earlier identification of immunotherapy candidates. Furthermore, reliable IHC-based LS screening performed on EMB/C can guide patient management and genetic counseling in patients unable to undergo hysterectomy.
在过去的五到十年中，林奇综合征（LS）的子宫内膜癌（EC）普遍筛查已逐渐得到实施。大多数病理学家开始使用免疫组织化学（IHC）对错配修复蛋白（MMRPs）进行筛查，使用的标本包括术前采样（子宫内膜活检或刮宫术，EMB/C）或子宫切除术标本。我们报告了对 EMB/C 与子宫切除术标本用于 LS 筛查的 IHC 等效性的系统评估。
我们鉴定了 99 例诊断为子宫内膜样 EC 的患者，并对其诊断性 EMB/C 和配对的子宫切除术标本进行了 MMRPs MLH1、MSH2、MSH6 和 PMS2 的 IHC。每个标本的评分均为 MMRP 保留或 MMRP 缺失。
91 例 EMB/C 中有癌，而 8 例 EMB/C 仅显示复杂不典型增生（CAH）。所有 99 例子宫切除术标本均鉴定出癌。考虑到所有 99 例测试患者，EMB/C 和配对子宫切除术标本之间的 MMRP 表达模式的一致性为 100%。69 例保留了所有 4 种 MMRP，而 30 例为 MMRP 缺失（26 例 MLH1 和 PMS2 缺失，3 例 MSH2 和 MSH6 缺失，1 例 PMS2 缺失）。
在 EC 中进行 LS 筛查时，MMRP 的 IHC 可在 EMB/C 或子宫切除术标本上以相同的准确性进行。常规检测诊断性 EMB/C 可能会更早地发现 MMRP 缺陷，提高患者对遗传咨询的接受度，并有可能更早地确定免疫治疗候选者。此外，在无法进行子宫切除术的患者中，基于可靠的 IHC 的 LS 筛查可以指导患者管理和遗传咨询。
