• Katerina Kubelka Sabit Faculty of Medical Sciences, Goce Delcev University, Stip, Republic of North Macedonia
  • Deva Petrova Faculty of Medical Sciences, Goce Delcev University, Stip, Republic of North Macedonia
  • Julija Zhivadinoviкј Institute of Anatomy, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Dzangis Jashar Faculty of Medical Sciences, Goce Delcev University, Stip, Republic of North Macedonia
  • Vanja Filipovski Faculty of Medical Sciences, Goce Delcev University, Stip, Republic of North Macedonia


Lynch syndrome, endometrial cancer


Lynch syndrome (LS) is an autosomal dominant inherited disease defined by germline mutations in mismatch repair (MMR) genes, leading to a defective DNA MMR system. Patients with LS have predisposition to a spectrum of cancers, primarily colorectal cancer, but LS-associated endometrial cancer (LS-EC) is the most common extraintestinal cancer and occurs in 2% of LS patients. The most frequently mutated MMR genes are MLH1, MSH2, MSH6 and PMS2. Clinico-pathologic features of LS-EC are: early age of onset, lower body mass index, endometrioid type of carcinoma and lower uterine segment involvement. 

Recent studies support LS screening in every EC patient since MMR status is also part of the molecular subclassification of endometrial cancers. Screening methods include traditional clinical criteria and molecular techniques, such as MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1promoter methylation testing and gene sequencing. MSI can also be detected in sporadic tumors, through epigenetic events inactivating the MMR system.

Patients with diagnosed LS and their affected relatives should be closely monitored in order to prevent the development of other types of cancer. Patients with advanced recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) endometrial cancer can also benefit from immunotherapy.

We describe our 3-year experience in screening of Lynch syndrome in EC patients.


Lynch HT, Snyder CL, Shaw TG, Heinen CD, Hitchins MP. Milestones of Lynch syndrome: 1895-2015. Nat Rev Cancer 2015; 15(3): 181-194.

Tafe LJ. Targeted Next-Generation Sequencing for Hereditary Cancer Syndromes: A Focus on Lynch Syndrome and Associated Endometrial Cancer. J Mol Diagn JMD 2015; 17(5): 472-482.

Pellat A, Netter J, Perkins G, Cohen R, Coulet F, Parc Y, et al. [Lynch syndrome: What is new?]. Bull Cancer (Paris) 2019; 106(7-8): 647-655.

Bats AS, Rossi L, Le Frere-Belda MA, Narjoz C, Cournou C, Gosset M, et al. [Lynch syndrome and endometrial cancer]. Bull Cancer (Paris) 2017; 104(12): 1013-1021.

Xu Y, Li C, Zheng CZL, Zhang YQ, Guo TA, Liu FQ, et al. Comparison of long-term outcomes between Lynch syndrome and sporadic colorectal cancer: a propensity score matching analysis. BMC Cancer 2021; 21(1): 45.

Fiumicino S, Ercoli A, Ferrandina G, Hess P, Raspaglio G, Genuardi M, et al. Microsatellite instability is an independent indicator of recurrence in sporadic stage I-II endometrial adenocarcinoma. J Clin Oncol Off J Am Soc Clin Oncol 2001; 19(4): 1008-10014.

Resnick KE, Hampel H, Fishel R, Cohn DE. Current and emerging trends in Lynch syndrome identification in women with endometrial cancer. Gynecol Oncol 2009; 114(1): 128-134.

Backes FJ, Cohn DE. Lynch syndrome. Clin Obstet Gynecol 2011; 54(2): 199-214.

Llach J, Pellisé M, Monahan K. Lynch syndrome; towards more personalized management? Best Pract Res Clin Gastroenterol 2022; 58-59: 101790.

Biller LH, Syngal S, Yurgelun MB. Recent advances in Lynch syndrome. Fam Cancer 2019; 18(2): 211-219.

Bu R, Siraj AK, Parvathareddy SK, Iqbal K, Azam S, Qadri Z, et al. Lynch Syndrome Identification in Saudi Cohort of Endometrial Cancer Patients Screened by Universal Approach. Int J Mol Sci 2022; 23(20): 12299.

Manchana T, Ariyasriwatana C, Triratanachat S, Phowthongkum P. Lynch Syndrome in Thai Endometrial Cancer Patients. Asian Pac J Cancer Prev APJCP 2021; 22(5): 1477-1483.

Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 2008; 135(2): 419-428.

Bonadona V, Bonaïti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 2011; 305(22): 2304-2310.

Cerretelli G, Ager A, Arends MJ, Frayling IM. Molecular pathology of Lynch syndrome. J Pathol 2020; 250(5): 518-531.

Pauly N, Baert T, Schmutzler R, du Bois A, Schneider S, Rhiem K, et al. Modern day screening for Lynch syndrome in endometrial cancer: the KEM experience. Arch Gynecol Obstet 2021; 304(4): 975-984.

Dottino JA, Lu KH. Towards value-based universal Lynch syndrome identification in endometrial cancer patients. Gynecol Oncol 2016; 143(3): 451-452.

Bruegl AS, Kernberg A, Broaddus RR. Importance of PCR-based Tumor Testing in the Evaluation of Lynch Syndrome-associated Endometrial Cancer. Adv Anat Pathol 2017; 24(6): 372-378.

Lu KH, Daniels M. Endometrial and ovarian cancer in women with Lynch syndrome: update in screening and prevention. Fam Cancer 2013;12(2): 273-277.






Case Reports