Das Lynch-Syndrom als bedeutendes erbliches Tumorsyndrom

Neben dem hereditären Brust- und Eierstockkrebssyndrom ist das Lynch-Syndrom das häufigste erbliche Tumorsyndrom mit kolorektalen, gynäkologischen sowie Manifestationen an weiteren Organsystemen. Die sorgfältige ärztliche (Familien-) Anamnese ist vor allem im Hinblick auf die Früherkennung der prognostisch ungünstigen Kolorektalkarzinome sehr wichtig. Für assoziierte gynäkologische Tumoren sind Checkpoint-Inhibitoren vielversprechende Therapeutika.

Schlüsselwörter

Hereditäres Tumorsyndrom - HNPCC - Mismatch-Repair-Mutation - Endometriumkarzinom - Ovarialkarzinom - Kolorektalkarzinom - Checkpoint-Inhibitoren - Mikrosatelliteninstabilität - Lynch-Syndrom

• Literatur

• 1 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Diagnostik, Therapie und Nachsorge der Patientinnen mit Endometriumkarzinom, Langversion 1.0, 2018, AWMF Registernummer: 032/034-OL. Im Internet (Stand: 10.02.2020): http://www.leitlinienprogramm-onkologie.de/leitlinien/endometriumkarzinom/
• 2 Yurgelun MB, Hampel H. Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention. Am Soc Clin Oncol Educ Book 2018; 38: 101-109 doi:10.1200/EDBK_208341
• 3 Bercow AS, Eisenhauer EL. Screening and surgical prophylaxis for hereditary cancer syndromes with high risk of endometrial and ovarian cancer. J Surg Oncol 2019; 120: 864-872 doi:10.1002/jso.25645
• 4 Ryan NAJ, Glaire MA, Blake D. et al. The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis. Genet Med 2019; 21: 2167-2180 doi:10.1038/s41436-019-0536-8
• 5 Biller LH, Syngal S, Yurgelun MB. Recent advances in Lynch syndrome. Fam Cancer 2019; 18: 211-219 doi:10.1007/s10689-018-00117-1
• 6 Mills AM, Sloan EA, Thomas M. et al. Clinicopathologic Comparison of Lynch Syndrome-associated and “Lynch-like” Endometrial Carcinomas Identified on Universal Screening Using Mismatch Repair Protein Immunohistochemistry. Am J Surg Pathol 2016; 40: 155-165 doi:10.1097/PAS.0000000000000544
• 7 Xicola RM, Clark JR, Carroll T. et al. Implication of DNA repair genes in Lynch-like syndrome. Fam Cancer 2019; 18: 331-342 doi:10.1007/s10689-019-00128-6
• 8 Hüneburg R, Aretz S, Buttner R. et al. Empfehlungen zur Früherkennung, Risikoreduktion, Überwachung und Therapie bei Patienten mit Lynch-Syndrom – Current recommendations for surveillance, risk reduction and therapy in Lynch syndrome patients. Z Gastroenterol 2019; 57: 1309-1320 doi:10.1055/a-1008-9827
• 9 Møller P, Seppala T, Bernstein I. et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut 2017; 66: 464-472 doi:10.1136/gutjnl-2015-309675
• 10 Harter P, Hauke J, Heitz F. et al. Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1). PLoS One 2017; 12: e0186043 doi:10.1371/journal.pone.0186043
• 11 Crispens MA. Endometrial and ovarian cancer in lynch syndrome. Clin Colon Rectal Surg 2012; 25: 97-102 doi:10.1055/s-0032-1313780
• 12 Carcangiu ML, Radice P, Casalini P. et al. Lynch syndrome-related endometrial carcinomas show a high frequency of nonendometrioid types and of high FIGO grade endometrioid types. Int J Surg Pathol 2010; 18: 21-26 doi:10.1177/1066896909332117
• 13 McMeekin DS, Tritchler DL, Cohn DE. et al. Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol 2016; 34: 3062-3068 doi:10.1200/JCO.2016.67.8722
• 14 Rossi L, Le Frere-Belda MA, Laurent-Puig P. et al. Clinicopathologic Characteristics of Endometrial Cancer in Lynch Syndrome: A French Multicenter Study. Int J Gynecol Cancer 2017; 27: 953-960 doi:10.1097/IGC.0000000000000985
• 15 Gargiulo P, Della Pepa C, Berardi S. et al. Tumor genotype and immune microenvironment in POLE-ultramutated and MSI-hypermutated Endometrial Cancers: New candidates for checkpoint blockade immunotherapy?. Cancer Treat Rev 2016; 48: 61-68 doi:10.1016/j.ctrv.2016.06.008
• 16 Ferriss JS, Williams-Brown MY. Immunotherapy: Checkpoint Inhibitors in Lynch-Associated Gynecologic Cancers. Curr Treat Options Oncol 2019; 20: 75 doi:10.1007/s11864-019-0676-8
• 17 Cosgrove CM, Cohn DE, Hampel H. et al. Epigenetic silencing of MLH1 in endometrial cancers is associated with larger tumor volume, increased rate of lymph node positivity and reduced recurrence-free survival. Gynecol Oncol 2017; 146: 588-595 doi:10.1016/j.ygyno.2017.07.003
• 18 Dashti SG, Chau R, Ouakrim DA. et al. Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome. JAMA 2015; 314: 61-71 doi:10.1001/jama.2015.6789
• 19 Staff S, Aaltonen M, Huhtala H. et al. Endometrial cancer risk factors among Lynch syndrome women: a retrospective cohort study. Br J Cancer 2016; 115: 375-381 doi:10.1038/bjc.2016.193
• 20 Ryan NAJ, Evans DG, Green K. et al. Pathological features and clinical behavior of Lynch syndrome-associated ovarian cancer. Gynecol Oncol 2017; 144: 491-495 doi:10.1016/j.ygyno.2017.01.005
• 21 Woolderink JM, De Bock GH, de Hullu JA. et al. Characteristics of Lynch syndrome associated ovarian cancer. Gynecol Oncol 2018; 150: 324-330 doi:10.1016/j.ygyno.2018.03.060
• 22 Niskakoski A, Pasanen A, Porkka N. et al. Converging endometrial and ovarian tumorigenesis in Lynch syndrome: Shared origin of synchronous carcinomas. Gynecol Oncol 2018; 150: 92-98 doi:10.1016/j.ygyno.2018.04.566
• 23 Burleigh A, Talhouk A, Gilks CB. et al. Clinical and pathological characterization of endometrial cancer in young women: identification of a cohort without classical risk factors. Gynecol Oncol 2015; 138: 141-146 doi:10.1016/j.ygyno.2015.02.028
• 24 Stoll J, Rosenthal E, Cummings S. et al. No Evidence of Increased Risk of Breast Cancer in Women With Lynch Syndrome Identified by Multigene Panel Testing. JCO Precis Oncol 2020; 4: 51-60
• 25 Crosbie EJ, Ryan NAJ, Arends MJ. et al. The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome. Genet Med 2019; 21: 2390-2400 doi:10.1038/s41436-019-0489-y
• 26 Büttner R, Friedrichs N. Erblicher Darmkrebs bei Lynch-/HNPCC-Syndrom in Deutschland. Pathologe 2019; 40: 584-591 doi:10.1007/s00292-019-0643-y
• 27 Kahn RM, Gordhandas S, Maddy BP. et al. Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population?. Cancer 2019; 125: 3172-3183 doi:10.1002/cncr.32203
• 28 Ta RM, Hecht JL, Lin DI. Discordant loss of mismatch repair proteins in advanced endometrial endometrioid carcinoma compared to paired primary uterine tumors. Gynecol Oncol 2018; 151: 401-406 doi:10.1016/j.ygyno.2018.10.012
• 29 Emons G, Vordermark D. Adjuvant treatment for endometrial cancer. Curr Opin Oncol 2019; 31: 404-410 doi:10.1097/CCO.0000000000000558
• 30 Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF. Leitlinienprogramm Onkologie: S3-Leitlinie Diagnostik, Therapie und Nachsorge maligner Ovarialtumoren, Langversion 4.0, 2020. AWMF-Registernummer: 032/035OL. Im Internet (Stand: 10.02.2020): https://www.leitlinienprogramm-onkologie.de/leitlinien/ovarialkarzinom
• 31 Sun CC, Meyer LA, Daniels MS. et al. Womenʼs preferences for cancer risk management strategies in Lynch syndrome. Gynecol Oncol 2019; 152: 514-521 doi:10.1016/j.ygyno.2018.11.027
• 32 Stadler ZK, Robson ME. Inherited predisposition to endometrial cancer: moving beyond Lynch syndrome. Cancer 2015; 121: 644-647 doi:10.1002/cncr.29107
• 33 Mahdi H, Mester JL, Nizialek EA. et al. Germline PTEN, SDHB-D, and KLLN alterations in endometrial cancer patients with Cowden and Cowden-like syndromes: an international, multicenter, prospective study. Cancer 2015; 121: 688-696 doi:10.1002/cncr.29106
• 34 The American College of Obstetricians and Gynecologists. Hereditary Cancer Syndromes and Risk Assessment: ACOG COMMITTEE OPINION, Number 793. Obstet Gynecol 2019; 134: e143-e149 doi:10.1097/AOG.0000000000003562
• 35 de Jonge MM, Mooyaart AL, Vreeswijk MP. et al. Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report. Eur J Cancer 2017; 72: 215-225 doi:10.1016/j.ejca.2016.11.028
• 36 Pennington KP, Walsh T, Lee M. et al. BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. Cancer 2013; 119: 332-338 doi:10.1002/cncr.27720
• 37 Segev Y, Rosen B, Lubinski J. et al. Risk factors for endometrial cancer among women with a BRCA1 or BRCA2 mutation: a case control study. Fam Cancer 2015; 14: 383-391 doi:10.1007/s10689-015-9798-8
• 38 Shu CA, Pike MC, Jotwani AR. et al. Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations. JAMA Oncol 2016; 2: 1434-1440 doi:10.1001/jamaoncol.2016.1820
• 39 Saule C, Mouret-Fourme E, Briaux A. et al. Risk of Serous Endometrial Carcinoma in Women With Pathogenic BRCA1/2 Variant After Risk-Reducing Salpingo-Oophorectomy. J Natl Cancer Inst 2018; 110