Catena Ursula, Della Corte Luigi, Raffone Antonio, Travaglino Antonio, Lucci Cordisco Emanuela, Teodorico Elena, Masciullo Valeria, Bifulco Giuseppe, Di Spiezio Sardo Attilio, Scambia Giovanni, Fanfani Francesco
Division of Gynecologic Surgery, Department of Woman, Child and Public Health, Fondazione Policlinico Universitario Agostino Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.
Front Med (Lausanne). 2022 Aug 25;9:948509. doi: 10.3389/fmed.2022.948509. eCollection 2022.
Lynch Syndrome (LS) represents the hereditary condition that is most frequently associated with endometrial cancer (EC). The aim of this study is to assess the presence of Lynch Syndrome (LS) in young women with mismatch repair (MMR)-deficient atypical endometrial hyperplasia (AEH) and non-myoinvasive FIGO G1 endometrioid EC and its possible impact on the outcome of conservative treatment.
Six MMR-deficient cases identified from a previous cohort of 69 conservatively treated patients were selected to be screened for germline mutations in MMR genes. In each patient, the outcomes of conservative treatment for AEH and EEC, including response, relapse, progression, and pregnancy, were assessed.
Five out of 6 patients underwent genetic test for LS. Three out of these 5 patients showed a positive genetic test. Patient 1 showed the c.942 + 2 T>A heterozygous variant of mutation; after 12 months of complete response, she had relapse and progression of disease. Patient 4 showed the c.2459-1G>C variant of mutation; after complete response, she failed to achieve pregnancy; she had relapse after 24 months and underwent hysterectomy. Patient 6 showed the c.803 + 1 heterozygous variant of mutation; she had relapse of disease after 18 months from the first complete response and then underwent hysterectomy.
In this series, 3 out of 6 women with MMR-deficiency had LS. None of the patients achieved pregnancy, and those who responded to treatment had subsequent relapse of disease. Patients undergoing fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer should perform MMR immunohistochemical analysis in order to screen LS.
林奇综合征（LS）是最常与子宫内膜癌（EC）相关的遗传性疾病。本研究的目的是评估错配修复（MMR）缺陷的非典型子宫内膜增生（AEH）和非肌层浸润性FIGO G1级子宫内膜样EC的年轻女性中林奇综合征（LS）的存在情况及其对保守治疗结局的可能影响。
从先前一组69例接受保守治疗的患者中筛选出6例MMR缺陷病例，对其MMR基因进行种系突变筛查。评估每位患者AEH和EEC的保守治疗结局，包括反应、复发、进展和妊娠情况。
6例患者中有5例接受了LS基因检测。这5例患者中有3例基因检测呈阳性。患者1显示c.942 + 2 T>A杂合突变；在完全缓解12个月后，她出现疾病复发和进展。患者4显示c.2459-1G>C突变；完全缓解后，她未能成功妊娠；24个月后复发并接受了子宫切除术。患者6显示c.803 + 1杂合突变；首次完全缓解18个月后疾病复发，随后接受了子宫切除术。
在本系列研究中，6例MMR缺陷女性中有3例患有LS。所有患者均未成功妊娠，且对治疗有反应的患者随后出现疾病复发。因非典型子宫内膜增生和子宫内膜癌接受保留生育功能治疗的患者应进行MMR免疫组化分析以筛查LS。
