Expression of human telomerase reverse transcriptase mRNA in esophageal cancers and precancerous lesions

Abstract

Telomerase activity confers immortality to cells through stabilization of chromosomes and contributes to the development of most human cancers. Human telomerase reverse transcriptase (hTERT) is a catalytic subunit of telomerase. Expression of hTERT mRNA has been reported to be correlated with telomerase activity. The purpose of this study was to investigate localization of hTERT mRNA in human esophageal precancerous and cancerous lesions by in situ mRNA hybridization with avidin-biotin staining. Ki-67 immunoreactivity was also examined. We analyzed 51 squamous cell carcinomas, 9 dysplasias and 60 normal mucosae. The integrity of mRNA in each sample was verified with a poly-d(T)20 probe. Seventy-eight samples (65%), including 35 carcinomas, 4 dysplasias and 39 normal mucosae, contained intact mRNA. At the single-cell level, hTERT was expressed at high levels in both the cytoplasm and nucleus. In all cases, the majority of cancer and dysplastic cells showed high levels of hTERT expression. In all 39 normal mucosae, basal cells expressed hTERT mRNA, and this was also observed in infiltrating lymphocytes. The distribution of cells expressing hTERT was similar to that of Ki-67-positive cells. These results suggest that overexpression of hTERT mRNA may be correlated with proliferative activity reflected by Ki-67 immunoreactivity and is an early event in carcinogenesis of the esophagus.