Overexpression of hTERT in potentially malignant colorectal laterally spreading tumors

Abstract

Abstract. Human telomerase reverse transcriptase (hTERT) is the main subunit of the core enzyme telomerase, which consists of three subunits. Telomeres are essential for chromosomal stability and integrity, protecting the ends of chromosomes from degradation and preventing chromosomal end fusions and recombination. A loss of telomere function is a major mechanism for the generation of chromosomal abnormalities. Telomere shortening leads to mutations, chromosome rearrangements and translocations. Colorectal laterally spreading tumors (LSTs) are a special type of superficial colorectal tumor. They are considered to have a high malignancy potential. The aim of the present study was to characterize the expression of hTERT in an LST cell line and paraffin sections. Immunohistochemistry was utilized to examine the protein expression of hTERT in the LST cell line, 48 resected LSTs, 48 protruded-type colorectal adenomas (PAs) and 48 normal mucosa samples. Statistical analyses were applied to test the associations between hTERT expression and clinicopathological parameters. The present study demonstrated that the positive expression levels of hTERT in LSTs, PAs and normal mucosa were 60.4, 22.9 and 10%, respectively. Compared with polypi and normal mucosa, the expression levels of hTERT were significantly increased in LSTs. The expression of hTERT was also observed in the LST cell line. The expression of hTERT was significantly higher in LSTs, which may indicate a potential for malignancy. IntroductionColorectal laterally spreading tumors (LSTs) of the colon and rectum are defined as lesions >10 mm in diameter with a low vertical axis that extend laterally along the luminal wall (1). The clinical characteristics of LSTs include a flat and superficial growth pattern. Although LSTs are known as adenomas or 'pre-existing cancers', they have been hypothesized to have malignant potential. LSTs are divided into two macroscopic subtypes, flat (F)-type and protruded-type (2). Despite the distinctive biological behaviors of LSTs, a number of genetic alterations have been reported, including K-ras and p53 mutations and cyclooxygenase 2 overexpression (3-6). Wang et al (7) observed that the expression of E-cadherin, β-catenin, glycogen synthase kinase-3β (GSK-3β), cyclin D1 and c-myc was positive in LSTs. Human telomerase reverse transcriptase (hTERT/Hest2/TP2), the main subunit involved in telomerase reverse transcription, is considered as one of the most important proteins affecting telomerase activity (8,9). However, hTERT expression in LSTs has not been thoroughly studied. Thus, this study aimed to elucidate the expression levels of hTERT in LSTs, colorectal tumors with a high malignancy potential. Materials and methodsLST cell line. The novel LST cell line was obtained from the Department of Gastroenterology, Nan Fang Hospital, Affiliated Hospital of Nan Fang Medical University, China. The LST cell line was established from a human rectal villous adenoma obtained using endoscopic resection. A magnifying endoscope showed a flat...

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