PMID- 10640962 OWN - NLM STAT- MEDLINE DCOM- 20000216 LR - 20061115 IS - 0008-543X (Print) IS - 0008-543X (Linking) VI - 88 IP - 2 DP - 2000 Jan 15 TI - Precancerous hepatic nodules had significant levels of telomerase activity determined by sensitive quantitation using a hybridization protection assay. PG - 312-7 AB - BACKGROUND: Telomeric repeat amplification protocol using internal telomerase assay standard (ITAS) (conventional TRAP) has detected telomerase activity in various malignant tumors. With conventional TRAP, it is difficult to differentiate quantitatively low levels of telomerase activity between well-differentiated hepatocellular carcinomas (HCCs) and dysplastic nodules because of quantitative limitation. To apply a telomerase assay for differential diagnosis, we used a hybridization protection assay combined with TRAP (TRAP/HPA). This combination had better sensitivity and wider linearity than conventional TRAP. METHODS: TRAP/HPA was applied for quantitative measurement of telomerase activity in various hepatic tissues. Telomerase activity was evaluated in 10 precancerous hepatic nodules, 17 well-differentiated HCCs, 19 moderately differentiated HCCs, 5 poorly differentiated HCCs, 22 nontumorous chronic hepatic disease samples, and 2 normal liver tissues. RESULTS: Telomerase activity in HCCs tended to increase according to the malignant transformation. The average relative telomerase activity in 0.6 microg protein, which was expressed as cell equivalent activity of MKN-1, a gastric carcinoma cell line, was 8.5 in precancerous hepatic nodules, 87 in well-differentiated HCCs, 265 in moderately differentiated HCCs, 447 in poorly differentiated HCCs, and 0.4 in nontumorous hepatic tissues, including chronic liver diseases. CONCLUSIONS: TRAP/HPA was sensitive enough to distinguish the telomerase activity in precancerous hepatic nodules from that in other lesions. Telomerase activity in precancerous hepatic nodules was higher than that in nontumorous hepatic tissues. However, the activity in precancerous hepatic nodules was lower than that in well-differentiated HCCs, although statistically not significant. The authors suggest that precancerous hepatic nodules with telomerase activity above the diagnostic cutoff level (twice the highest activity in nontumorous hepatic tissues, or the 2 cell equivalent activity of MKN-1) should be treated as malignancy. CI - Copyright 2000 American Cancer Society. FAU - Takaishi, H AU - Takaishi H AD - First Department of Internal Medicine, Hiroshima School of Medicine, Hiroshima, Japan. FAU - Kitamoto, M AU - Kitamoto M FAU - Takahashi, S AU - Takahashi S FAU - Aikata, H AU - Aikata H FAU - Kawakami, Y AU - Kawakami Y FAU - Nakanishi, T AU - Nakanishi T FAU - Nakamura, Y AU - Nakamura Y FAU - Shimamoto, F AU - Shimamoto F FAU - Kajiyama, G AU - Kajiyama G FAU - Ide, T AU - Ide T LA - eng PT - Journal Article PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (DNA Primers) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - DNA Primers MH - Humans MH - Liver/enzymology MH - Liver Neoplasms/*enzymology MH - *Nucleic Acid Amplification Techniques MH - *Nucleic Acid Hybridization MH - Precancerous Conditions/*enzymology MH - Sensitivity and Specificity MH - Telomerase/analysis/*metabolism EDAT- 2000/01/21 09:00 MHDA- 2000/02/19 09:00 CRDT- 2000/01/21 09:00 PHST- 2000/01/21 09:00 [pubmed] PHST- 2000/02/19 09:00 [medline] PHST- 2000/01/21 09:00 [entrez] AID - 10.1002/(SICI)1097-0142(20000115)88:2<312::AID-CNCR10>3.0.CO;2-R [pii] PST - ppublish SO - Cancer. 2000 Jan 15;88(2):312-7.