Practice patterns for Lynch syndrome-associated endometrial cancer management in Korea

Objectives: This study aimed to investigate practice patterns for the management of LS-associated endometrial cancer among Korean gynecologic oncologists. Material and methods: Members of the Korean Society of Gynecologic Oncology were surveyed using a self-administered questionnaire regarding their knowledge and clinical management of LS by paper or e-mail. Results: Of the 49 participants, the median age was 43 years (range, 30–75). The respondents worked mainly in Seoul (25/49, 51.0%) and the capital area (16/49, 32.7%). The average score on LS knowledge assessment was 3.8 (range, 0–8) with a maximum score of 8. The following tools were used by the respondents for the identification of inherited endometrial cancer: obtaining of family history (46.7%), immunohistochemistry (IHC) test for four mismatch repair (MMR) genes (38.8%), and microsatellite instability (MSI) test (8.2%) for all endometrial cancer patients. The indications for recommending the germline MMR gene test were endometrial cancer with a family history (5/49, 10.2%), patients who met the Amsterdam II criteria (32/49, 65.3%), abnormal IHC test results (13/49, 26.5%), and abnormal MSI test results (8/49, 16.3%). Approximately half of the respondents recommended cascade testing (28/49, 57.1%) to the family of the proband and recommended risk-reducing management for MMR mutation carriers (27/49, 55.1%). Conclusion: Gynecologic oncologists in Korea are not aware of genetic risk assessment and patient counseling about LS. Therefore, it is necessary to educate physicians and develop guidelines in this regard.

Endometrial neoplasms; Lynch syndrome; Practice pattern

[1] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA: A Cancer Journal for Clinicians. 2021; 71: 7–33.

[2] Lim MC, Won YJ, Ko MJ, Kim M, Shim SH, Suh DH, et al. Incidence of cervical, endometrial, and ovarian cancer in Korea during 1999-2015. Journal of Gynecologic Oncology. 2019; 30: e38.

[3] Jung K, Won Y, Hong S, Kong H, Lee ES. Prediction of Cancer Incidence and Mortality in Korea, 2020. Cancer Research and Treatment. 2020; 52: 351–358.

[4] Hinchcliff EM, Bednar EM, Lu KH, Rauh-Hain JA. Disparities in gynecologic cancer genetics evaluation. Gynecologic Oncology. 2019; 153: 184–191.

[5] Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993; 75: 1027–1038.

[6] Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA, et al. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994; 263: 1625–1629.

[7] Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993; 75: 1215–1225.

[8] Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, et al. Mutation in the DNA mismatch repair gene homo-logue hMLH1 is associated with hereditary nonpolyposis colon cancer. Nature. 1994; 368: 258–261.

[9] Hendriks YMC, Jagmohan-Changur S, van der Klift HM, Morreau H, van Puijenbroek M, Tops C, et al. Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome). Gastroenterology. 2006; 130: 312–322.

[10] Tutlewska K, Lubinski J, Kurzawski G. Germline deletions in the EPCAM gene as a cause of Lynch syndrome - literature review. Hereditary Cancer in Clinical Practice. 2013; 11: 9.

[11] Lin KM, Shashidharan M, Thorson AG, Ternent CA, Blatchford GJ, Christensen MA, et al. Cumulative incidence of colorectal and extracolonic cancers in MLH1 and MSH2 mutation carriers of hereditary nonpolyposis colorectal cancer. Journal of Gastroin-testinal Surgery. 1998; 2: 67–71.

[12] Barrow E, Hill J, Evans DG. Cancer risk in Lynch Syndrome. Familial Cancer. 2013; 12: 229–240.

[13] Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, et al. The clinical phenotype of Lynch syndrome due to germline PMS2 mutations. Gastroenterology. 2008; 135: 419–428.

[14] Dominguez-Valentin M, Sampson JR, Seppälä TT, Ten Broeke SW, Plazzer JP, Nakken S, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genetics in Medicine. 2020; 22: 15–25.

[15] Lim MC, Seo S, Kang S, Seong M, Lee B, Park S. Hereditary nonpolyposis colorectal cancer/Lynch syndrome in Korean patients with endometrial cancer. Japanese Journal of Clinical Oncology. 2010; 40: 1121–1127.

[16] Yoon SN, Ku J, Shin Y, Kim K, Choi J, Jang E, et al. Hereditary nonpolyposis colorectal cancer in endometrial cancer patients. International Journal of Cancer. 2008; 122: 1077–1081.

[17] Lu KH, Dinh M, Kohlmann W, Watson P, Green J, Syngal S, et al. Gynecologic Cancer as a “Sentinel Cancer” for Women with Hereditary Nonpolyposis Colorectal Cancer Syndrome. Obstetrics & Gynecology. 2005; 105: 569–574.

[18] NCCN. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Genetic/Familial High-Risk Assessment: Colorectal. version 1.2021-May 11. 2021. Available at: https://www.nc cn.org/professionals/physician_gls/pdf/genetics_colon.pdf (Accessed: 12 May 2021).

[19] Lee HJ, Choi MC, Jang J, Jung SG, Park H, Joo WD, et al. Clinicopathologic characteristics of double primary endometrial and colorectal cancers in a single institution. Journal of Obstetrics and Gynaecology Research. 2018; 44: 944–950.

[20] Song T, Kim MK, Lee Y, Choi CH, Kim T, Lee J, et al. Women with double primary cancers of the colorectum and endometrium: do they have Lynch syndrome? European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2016; 199: 208–212.

[21] Vasen HF. Clinical diagnosis and management of hereditary colorectal cancer syndromes. Journal of Clinical Oncology. 2000; 18: 81S–92S.

[22] Barnetson RA, Tenesa A, Farrington SM, Nicholl ID, Cetnarskyj R, Porteous ME, et al. Identification and survival of carriers of mutations in DNA mismatch-repair genes in colon cancer. New England Journal of Medicine. 2006; 354: 2751–2763.

[23] Samadder NJ, Smith KR, Wong J, Thomas A, Hanson H, Boucher K, et al. Cancer Risk in Families Fulfilling the Amsterdam Criteria for Lynch Syndrome. JAMA Oncology. 2017; 3: 1697–1701.

[24] Hendriks YMC, de Jong AE, Morreau H, Tops CMJ, Vasen HF, Wijnen JT, et al. Diagnostic approach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma): a guide for clinicians. CA: A Cancer Journal for Clinicians. 2006; 56: 213–225.

[25] Moreira L, Balaguer F, Lindor N, de la Chapelle A, Hampel H, Aaltonen LA, et al. Identification of Lynch syndrome among patients with colorectal cancer. Journal of the American Medical Association. 2012; 308: 1555–1565.

[26] Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. Journal of Clinical Oncology. 2020; 38: 1–10.

[27] Petrelli F, Ghidini M, Ghidini A, Tomasello G. Outcomes Following Immune Checkpoint Inhibitor Treatment of Patients with Microsatellite Instability-High Cancers: A Systematic Review and Meta-analysis. JAMA Oncology. 2020; 6: 1068–1071.

[28] Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357: 409–413.