UO Anatomia Patologica, ASST Settelaghi, Ospedale di Circolo.
Centro di ricerca dei tumori eredo-familiari.
Eur J Cancer Prev. 2022 Jul 1;31(4):369-376. doi: 10.1097/CEJ.0000000000000711. Epub 2021 Sep 13.
Endometrial carcinoma represents a sentinel cancer for Lynch syndrome (LS) identification. It is crucial to highlight how other types of tumors can arise in the gynecological tract acting as sentinel tumors in LS patients.Up to now, no established LS patient management strategy has incorporated the presence of these additional candidate sentinel tumors to improve the prevention and management of LS tumors.
In order to investigate the involvement of the most frequent gynecological cancers in gynecological cancers, we studied different subsets of gynecological cancers using both somatic approaches, including mismatch repair (MMR) gene immunohistochemical expression, microsatellite instability, and germline analyses ofMSH2, MSH6, MLH1, PMS2 and EPCAM genes.A total of 261 patients referring to the Cancer Genetic Counselling Service of our institution were included in the study. In detail, our series was composed of 131 patients affected by uterus cancers including endometrial, isthmus and non-HPV endocervical carcinomas, 113 patients affected by ovarian cancers and 17 patients affected by synchronous endometrial/ovarian carcinomas (SEOC).In addition, we studied 115 cases of endometrial cancers identified by 2 years of universal testing (endometrial cancers/UTs) using IHC analysis of four MMR proteins.
The incidence of MMR defective gynecological cancers ranged from 7.1 to 47.1% depending on cancer site and selection. LS patients carriers of pathogenetic MMR variants were identified in 19.8% of uterus cancers, 35.3% of SEOC, 4.4% of ovarian cancers. In addition, pathogenetic MMR variants were identified in 4.3% of endometrial cancers/universal testing investigated with universal screening.In conclusion, gynecological cancers are heavily involved in LS and our study shows that MMR screening using immunohistochemical pattern and MSI analysis of endometrial and ovarian cancers as well as of rare entities such as non-HPV related endocervical cancers and synchronous endometrial and ovarian cancers are sentinels for LS.Tumor testing approach improves early identification of MMR defective gynecological cancers and this is an effective strategy to detect high-risk patients and to offer them and their relatives personalized cancer prevention.
子宫内膜癌是林奇综合征（LS）识别的标志性癌症。重要的是要强调其他类型的肿瘤如何在妇科生殖道中出现，作为 LS 患者的标志性肿瘤。到目前为止，还没有建立 LS 患者管理策略，将这些额外的候选标志性肿瘤纳入其中，以改善 LS 肿瘤的预防和管理。
为了研究妇科癌症中最常见的癌症的参与情况，我们使用体细胞方法研究了不同的妇科癌症亚组，包括错配修复（MMR）基因免疫组化表达、微卫星不稳定性和 MSH2、MSH6、MLH1、PMS2 和 EPCAM 基因的种系分析。共纳入 261 例来自我们机构癌症遗传咨询服务的患者进行研究。具体来说，我们的系列由 131 例子宫癌患者组成，包括子宫内膜癌、子宫峡部癌和非 HPV 宫颈内腺癌，113 例卵巢癌患者和 17 例同步子宫内膜/卵巢癌（SEOC）患者。此外，我们还研究了 115 例通过两年通用检测（子宫内膜癌/UTs）确定的子宫内膜癌病例，使用四种 MMR 蛋白的免疫组化分析。
根据癌症部位和选择，MMR 缺陷型妇科癌症的发生率从 7.1%到 47.1%不等。在子宫癌、SEOC、卵巢癌中分别发现了 19.8%、35.3%和 4.4%的携带致病性 MMR 变异的 LS 患者。此外，在通过通用筛查进行的通用检测中，还发现了 4.3%的子宫内膜癌/UTs 中存在致病性 MMR 变异。总之，妇科癌症与 LS 密切相关，我们的研究表明，使用免疫组化模式和子宫内膜癌和卵巢癌的 MSI 分析以及罕见实体，如非 HPV 相关宫颈内腺癌和同步子宫内膜和卵巢癌对 MMR 进行筛查，是 LS 的哨兵。肿瘤检测方法可提高 MMR 缺陷型妇科癌症的早期识别，这是发现高危患者并为其及其亲属提供个性化癌症预防的有效策略。
