Lynch syndrome (hereditary non-polyposis colorectal cancer) and endometrial carcinoma

Abstract

Women with hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome have a high risk for endometrial cancer (EC) and frequently present with a gynaecological cancer as their first or sentinel malignancy. Identification of these patients is important given their personal and family risk for synchronous and metachronous tumours. Modalities to detect ECs for the possibility of HNPCC include microsatellite instability assay, immunohistochemistry for DNA mismatch repair proteins, MLH1 promoter hypermethylation assay and mutational analysis of DNA mismatch repair genes. The revised Bethesda guidelines provide screening criteria for HNPCC in colorectal cancers (CRCs). However, there are currently no such screening recommendations for women with endometrial carcinoma. While age and family history are useful screening criteria, their sensitivity has been shown to be low for detection of HNPCC in EC. Expansion of these criteria to include tumour morphology (presence of tumour infiltrating lymphocytes and tumour heterogeneity including dedifferentiated/undifferentiated ECs) and topography (lower uterine segment localisation) as well as presence of synchronous ovarian clear cell carcinomas may significantly enhance the detection of patients with EC at risk for HNPCC. Consideration should be given to incorporating these screening criteria into a revision of the Bethesda guidelines for detecting EC patients at highest risk for HNPCC.

Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR)

“…85 It has been suggested that, in a women with an endometrial carcinoma, the presence of a synchronous ovarian clear cell carcinoma may be an indicator of LS. 86 …”

Genomic profiling identifies GPC5 amplification in association with sarcomatous transformation in a subset of uterine carcinosarcomas

“…It should be noted that 4 of 22 cases were mismatch repair‐ and ARID1A‐deficient, raising concern that they may in fact represent de‐differentiated endometrial carcinomas 12, rather than carcinosarcoma sensu stricto . In addition, with only a single tumour sample sequenced per case, carcinoma and sarcoma components were not directly compared, precluding analysis of intratumour heterogeneity and the relationship between genetic alterations and histomorphology.…”

Hereditary Endometrial Carcinoma

“…MSI analysis has some limitations when used to detect LSassociated endometrial cancers. Many, but not all the ECs that are diagnosed in LS are MSI-H, while most, but not all MSI-H endometrial cancers are sporadic (Garg & Soslow, 2009). Thus, MSI analysis may fail to detect some LS-associated ECs, while it may turn out positive in a large percentage of sporadic ECs.…”