Significance of cytoplasmic expression of telomerase reverse transcriptase in patients with hepatocellular carcinoma undergoing liver resection

Abstract

Telomerase reverse transcriptase (TERT) is reportedly expressed in various types of cancer. However, to the best of our knowledge, the significance of subcellular expression of TERT in hepatocellular carcinoma (HCC) has not been evaluated in detail. The present study evaluated TERT expression in resected HCC tumor tissues using immunohistochemistry. TERT expression was assessed in both the cytoplasm and the nucleus of HCC cells. The associations between TERT expression and clinical characteristics, including expression levels of DNA-dependent protein kinase catalytic unit (DNA-PKcs) and 8-hydroxyganosine (8-OHdG), were investigated. Among the 135 HCCs, TERT expression was positive only in the cytoplasm in 86 tumors (63.7%), was positive only in the nucleus in 3 tumors (2.2%), was positive in both the cytoplasm and the nucleus in 5 tumors (3.7%) and was negative in 41 tumors (30.4%). Similar results were confirmed using another antibody for TERT. Cytoplasmic TERT expression was markedly associated with hepatitis B surface antigen, poor tumor differentiation, and expression levels of DNA-PKcs and 8-OHdG. However, TERT expression in the cytoplasm or in the nucleus was not significantly associated with the overall or recurrence-free survival periods. In conclusion, TERT was mainly expressed in the cytoplasm of HCC tissues. Cytoplasmic TERT expression was closely associated with hepatitis B virus-related HCC and DNA-PKcs expression, as well as oxidative stress.

Nuclear and Cytoplasmic hTERT, Tumor-Infiltrating Lymphocytes, and Telomere Elongation Leukocytes Are Independent Factors in the Response to Neoadjuvant Treatment in HER2-Enriched Breast Cancer

“…However, in hepatocellular carcinomas, the marking was predominantly and exclusively cytoplasmic in 86/135 (64%), while only 3/135 (2.2%) were associated with nuclear marking. Furthermore, in these cases cytoplasmic labeling was associated with the presence of hepatitis B surface antigen ( p = 0.007) and poor cell differentiation ( p = 0.043) [ 42 ].…”

Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients

“…We observed a strong cytoplasmic expression of TERT in the PGCC found in urine samples. Cytoplasmic expression of TERT was already observed in non-clear cell and clear cell hepatocellular carcinoma [ 34 , 35 ], cervical cancer [ 36 ], prostate cancer [ 37 ], and urothelial carcinoma [ 33 ], suggesting possible telomere-independent functions of TERT under conditions of environmental stress such as hypoxia and oxidative stress. As a matter of fact, PGCC are thought to be generated in response to stress conditions.…”