Abstract 1759: Immunohistochemical detection of human telomerase reverse transcriptase in human cholangiocarcinoma and risk condition.

Background/Aims: Telomerase activation plays a critical role in several human carcinogenesis through the maintenance of telomeres. The catalytic subunit of telomerase is human telomerase reverse transcriptase (hTERT), whose expression is the critical determinant of telomerase activity. Studies on hTERT in human cholangiocarcinoma (ChC) are rare, and there are no immunohistochemical studies on the correlations with its expressions and ChC patient9s clinicopathological parameters. Methods : HTERT Immunoreactivity was measured in cancerous parenchyma of 28 archival cases of human cholangiocarcinoma (ChC) compared with hyperplastic small biliary ducts in surrounding non-neoplastic liver. And hTERT immunoreactivity was also assessed in both large and small hyperplastic biliary ducts (HBDs) in 9 archival cases of primary sclerosing cholangitis (PSC), which is risk condition for human cholangiocarcinogenesis. Measurements of intrahepatic biliary duct sizes and quantitative microdensitometry measurements of immunostaining intensities were determined using a color video image analysis system. Micro-optical density values related to a standard optical density curve were generated for each set of measurements, using arbitrary units of immunostaining intensity ranging from 0 (nondetectable) to 255 (highest intensity). Results : HTERT immunoreactivity was presented in nuclei of ChC and PSC cells. Mean micro-optical density values for hTERT in tumorous cells were almost 8-fold greater than that measured in small HBDs in surrounding non-tumorous liver within the same tissue sections. Although there was no significantly difference of tumor differentiation in hTERT expression, its expression was stronger in tubular type than in papillary type and in tubulopapillary type. In PSC cases, hTERT expression was significantly stronger in large HBDs (>500μm cross-sectional diameter) than in small HBDs ( Conclusion : Our findings suggest that hTRET protein in human ChC may emerge at a early stage in the progression of the malignant process. The results also suggest hTERT as potentially important targets relevant to chemoprevention or adjunct therapy of ChC. Citation Format: Kanenori Endo, Shunichi Tsujitani, Miwa Yoshimoto, Jyoji Watanabe, Naruo Tokuyasu, Teruhisa Sakamoto, Takuji Naka, Yasuaki Hirooka, Masahide Ikeguchi. Immunohistochemical detection of human telomerase reverse transcriptase in human cholangiocarcinoma and risk condition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1759. doi:10.1158/1538-7445.AM2013-1759