Telomerase as a tool for the differential diagnosis of human hepatocellular carcinoma

BACKGROUND. Telomerase activation is thought to be essential for the immortality of cancer cells. We measured telomerase activity in human liver samples, including hepatocellular carcinoma (HCC), and evaluated this assay as a tool for the diagnosis of HCC using 21-gauge (21-G)-needle biopsy specimens. METHODS. Ninety-four liver samples (27 HCC, 27 liver cirrhosis, 37 chronic hepatitis, and 3 normal liver) that were surgically resected or biopsied with a 12-gauge Silverman needle and 13 HCC samples that were biopsied with a 21-G needle were analyzed for telomerase activation. RESULTS. Eleven of 29 (38%) tumor-bearing liver samples were weakly telomerase- positive, whereas telomerase activity was observed infrequently in nontumor- bearing liver samples (6 of 35; 17%) and in normal liver samples (0 of 3; 0%). The positivity of surgical samples for well differentiated, moderately differentiated, and poorly differentiated HCC was 88% (7 of 8), 87% (13 of 15), and 0% (0 of 2), respectively. In telomerase-positive HCC, 43%, (3 of 7) of well differentiated samples were weakly positive, whereas 92% (12 of 13) of moderately differentiated samples were strongly positive. The difference in the tumor sizes and viral marker status did not affect the activity. The telomerase activity of the 21-G-needle biopsied specimens showed no significant difference from that of the surgical samples. The positive incidence of 21-G specimens was 80% (8 of 10) and 100% (2 of 2) in well differentiated HCC and moderately differentiated HCC, respectively. CONCLUSIONS. An incremental positivity of telomerase was observed during hepatocarcinogenesis. The use of this assay in 21-G-needle biopsy specimens may be useful in clinical examination.