Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study

Abstract

Microsatellite instability (MSI) is a mutator phenotype that results from a defective mismatch repair (MMR) pathway. The present study examined the incidence of MSI and loss of heterozygosity (LOH) according to five markers from the panel of the National Cancer Institute (NCI) in 38 colorectal cancer (CRC) patients from the United Arab Emirates (UAE). MSI and LOH were analyzed using fragment analyses in a multiplex PCR setting on a capillary array electrophoresis platform. The expression of the MMR proteins, hMLH1 and hMSH2, was analyzed using immunohistochemistry. The cohort consisted of 17 females (44.7%) and 21 males (55.3%) with mean ages of 59.9 and 63.3 years, respectively. The overall MSI incidence was 31.3% (95% CI, 16.1–50.0), and included three patients with high MSI (MSI-H; 9.4%; 95% CI, 2.0–25.0) and seven patients with low MSI (MSI-L; 21.9%; 95% CI, 10.7–39). LOH was detected in three patients, while the remaining 25 patients (65.8%) showed no instability and were therefore classified as microsatellite stable (MSS). MSI was detected in the following screened markers: Bat25 in seven patients, Bat26 in three patients, adenomatous polyposis coli (APC; D5S346) in five patients, AFM093xh3 (D2S123) in two patients and Mfd15 (D17S250) in three patients. Of the five MSI-positive patients, four (80%) were evidently younger, aged 38, 48, 49 and 59 years, respectively. The MSI-H incidence (9.4%) was lower compared with that of other ethnic groups. In terms of the MMR proteins, hMLH1 expression was deficient in seven patients, of whom three were MSI-H patients, and hMSH2 was deficient in three patients. Fisher’s exact test showed significant associations between hMLH1 and MSI when classified as MSS, MSI-L or MSI-H (P=0.0003). No such association was observed with abnormal MMR protein expression, age, cancer stage or gender.