TELOMERASE ACTIVITY IN PRECANCEROUS HEPATIC NODULES

BACKGROUND. Recent studies have demonstrated that telomerase, a revers e transcriptase linked to cellular ''immortalization,'' is activated i n a variety of malignant human tumors. This study was conducted to det ermine whether telomerase activity represents a marker of malignant tr ansformation in precancerous (dysplastic) nodules arising in patients with cirrhosis. METHODS. Telomerase activity was evaluated in frozen t issue samples of 14 cirrhotic liver specimens and 30 large nodular les ions contained therein, including 13 large regenerative nodules/low gr ade dysplastic nodules, 10 high grade dysplastic nodules, and 7 hepato cellular carcinomas (HCCs). A modified telomeric repeat amplification protocol was used. RESULTS. There was a clear-cut difference in telome rase activity levels between HCC (positive or strongly positive) and c irrhotic liver samples (weakly positive or negative). The majority of large noncancerous nodules (86%) exhibited telomerase activity levels similar to HCCs. However, such activity was not limited to dysplastic lesions but also was detected in some large regenerative nodules. CONC LUSIONS. These findings suggest that telomerase activation is an early event in large nodule formation in cirrhosis, which may facilitate th e action of other factors in the process of carcinogenesis. Telomerase activity in large hepatic nodules is not always indicative of maligna nt transformation. (C) 1998 American Cancer Society.