Abstract. The function of microsatellite instability (MSI) and the optimal panel of markers for epithelial ovarian cancer (EOC) are not well established. This study aimed to use the National Cancer Institute (NCI) markers BAT25, BAT26, D2S123, D5S346 and D17S250 to evaluate MSI in patients with ovarian serous cystadenocarcinoma, compared with ovarian serous cystadenoma and normal ovaries. A total of 37 patients were divided into three groups, as follows: cystadenocarcinoma (n=13), cystadenoma (n=10) and normal ovaries (n=14). DNA was extracted with TRIzol and quantified by spectrophotometry. MSI was evaluated by polymerase chain reaction (PCR), and classified as high (MSI-H), low (MSI-L) or stable (MSS). FIGO staging was I/II in 23.1% and III/IV in 76.9% of the cystadenocarcinoma group. Polymorphisms were found using at least one marker in 32 women, and were observed with D2S123 (83.7%), D17S250 (81.1%), D5S346 (72.9%), BAT25 (21.6%) and BAT26 (16.2%) markers. In the cystadenocarcinoma group, BAT25, BAT26, D2S123, D5S346 and D17S250 markers were positive in 30.8, 76.9, 53.8, 69.2 and 69.2% of patients, respectively. The same markers were positive in 30, 50, 40, 60 and 30% of the cystadenoma group, and 50, 71.4, 71.4, 64.3 and 63.3% in the normal ovary group, respectively. MSI-H was present in 84.6, 60 and 78.6% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. MSI-L was detected in 0, 30 and 7.1%, and MSS was identified in 15.4, 10 and 14.3% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. The frequency of MSI in both benign epithelial ovarian neoplasms and in normal ovaries was high, as well as in EOC, with no statistically significant difference between the groups. This suggests that MSI may arise as a consequence of the ovulatory process, and not solely as a feature of malignant ovarian tumors.
IntroductionEpithelial ovarian cancer (EOC) has a high mortality rate (1); it is the leading cause of death among gynecological tumors, and the fourth leading cause of cancer-related mortality among women in the United States (2). Due its nonspecific symptoms and lack of effective screening methods (3), approximately two-thirds of cases are diagnosed in stages III and IV, with a five-year survival rate of 10-20% (4,5). Approximately 90% of ovarian tumors originate from epithelial cells (6,7). The mortality rate has not changed in the last two decades (8).A group of enzymes known as the DNA mismatch repair (MMR) system is responsible for repairing mutations. Hereditary nonpolyposis colorectal cancer (HNPCC) is the third leading cause of hereditary ovarian cancer, and is caused by mutations in genes of the MMR system. One of the consequences of deficient MMR is microsatellite instability (9), which carries somatic mutations in tumor suppressor genes, oncogenes, apoptosis and detoxification genes, and is involved in both the initiation and progression of tumors (10).HNPCC has been studied using a panel of five National Cancer Institute (NCI) markers, which includes two mono...