open access: Gynecologic Oncology Case Reports - A case of endometrial cancer in the context of a BRCA2 mutation and double heterozygosity for Lynch syndrome

ScienceDirect.com - Gynecologic Oncology Case Reports - A case of endometrial cancer in the context of a BRCA2 mutation and double heterozygosity for Lynch syndrome

 "....While endometrial cancer diagnosed under the age of 50 is not included in the Revised Bethesda Guideline, evidence suggests that these individuals should be evaluated for Lynch syndrome (Resnick et al., 2009). The patient presented was diagnosed with endometrial cancer at the age of 41 and genetic testing revealed triple heterozygosity for BRCA2, MLH1 and MSH6 mutations."

 Introduction

Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is an autosomal dominant cancer susceptibility syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, MLH1, MSH2, and less frequently MSH6 and PMS2. MMR mutation carriers are predisposed primarily to colorectal cancer and endometrial cancer, with an increased frequency of stomach, ovary, pancreas, upper urinary tract, brain, small bowel, and skin consistently reported. This hereditary syndrome accounts for approximately 2–3% of colorectal cancers and 1–4% of endometrial cancers in the United States (Lynch and de la Chapelle, 2003). Depending on the MMR gene involved, women with Lynch syndrome can have up to an 80% lifetime risk of developing colorectal cancer, and a 20–60% risk of endometrial cancer.

Germline mutations in BRCA1 or BRCA2 (BRCA1/2) cause hereditary breast ovarian cancer syndrome. Female carriers of BRCA1/2 mutations have excessive risks for both breast and ovarian cancer, with lifetime breast cancer estimates ranging from 45% to 84%, and lifetime ovarian cancer estimates ranging from 11% to 62%, depending upon the population studied. BRCA1/2 kindreds are also noted to have an increased frequency of prostate cancer, and in BRCA2 kindreds, increased frequencies of pancreatic cancer and melanoma are observed. The frequency of BRCA1 or BRCA2 mutations in the general population is estimated to be 1 in 300 to 1 in 800, respectively (King et al., 2003).

While there are kindreds with more than one cancer susceptibility syndrome and/or mutation reported in the literature ( [Thiffault et al., 2004] and [Smith et al., 2008]), they are not often encountered in routine clinical settings........

Highlights

► Endometrial cancer with BRCA2 mutation and double heterozygosity for Lynch syndrome.
► Loss of MLH1 and PMS2 by immunohistochemical stain.
► MSH1 and MSH6 gene mutations by genomic sequencing.