Association of Global DNA Hypomethylation with Clinicopathological Variables in Colonic Tumors of Iraqi Patients

BACKGROUND/AIM: Colorectal cancer (CRC) ranks sixth among the most common 10 cancers in Iraq. It is a foremost public health dilemma and there is improved interest in understanding the fundamental principles of its molecular biology. DNA methylation in cancer has become the issue of passionate investigation. As compared with normal cells, the malignant cells show major disruptions in their DNA methylation patterns. We aimed to assess the association of global DNA hypomethylation in colonic adenomas and carcinomas of Iraqi patients, measured by immunohistochemistry of 5-methylcytosin, with different clinicopathological variables. PATIENTS AND METHODS: Thirty tissue paraffin blocks from patients with colorectal adenomas, 30 tissue paraffin blocks from patients with colorectal adenocarcinomas, and 30 samples of apparently normal colonic tissue taken from autopsy cases as a control group were included in the present study. From each block, two sections of 5 μm thickness were taken, one section was stained with Hematoxylin and Eosin for revision of histopathological diagnosis and one section was immunohistochemically stained for 5-methylcytosine (5mC) and digitally analyzed by AperioImageScope software. RESULTS: The mean digital value of 5mC immunohistochemical expression was sequentially decreased during neoplastic progression from normal colonic tissue into adenoma and then to carcinoma. The mean digital value of 5mC expression was significantly lower in large size adenomas (≥1 cm), and those with severe dysplasia. Concerning carcinoma cases, 5mC expression was significantly lower in stage C2. CONCLUSIONS: The immunohistochemical evaluation of 5mC yields refined information on colorectal tumor biology in adenoma and carcinoma. Global DNA hypomethylation reflected by low immunohistochemical expression of 5-mC is associated with advanced colorectal adenomatous polyps suggesting that it is an early event in colorectal carcinogenesis. Also this hypomethylation can reflect bad prognosis of patients with colorectal cancer by its correlation to higher tumor stage.