Nakashio R, Kitamoto M, Tahara H, Nakanishi T, Ide T, Kajiyama G
First Department of Internal Medicine, Hiroshima University School of Medicine, Minami-ku, Japan.
Int J Cancer. 1997 Apr 22;74(2):141-7. doi: 10.1002/(sici)1097-0215(19970422)74:2<141::aid-ijc1>3.0.co;2-z.
Precise diagnosis of well-differentiated hepatocellular carcinoma (HCC) is sometimes difficult to establish. Telomerase activity was examined by telomeric-repeat-amplification protocol (TRAP) in 37 HCC nodules smaller than 3 cm in diameter, including 24 fine-needle-aspiration biopsy specimens, 22 non-tumor chronic-liver-disease tissues (9 chronic hepatitis and 13 liver cirrhosis) and 3 normal liver tissues. Telomerase activity was assayed by serially diluted samples and quantitated by using an internal telomerase assay standard (ITAS). Telomerase activity was detected in all HCC and in 11 of 22 non-tumor chronic-liver-disease tissues. Normal liver samples had undetectable telomerase activity. Cut-off level of telomerase activity for its practical usage in HCC diagnosis was tentatively set for 0.6 microg liver protein/assay at 10-cell equivalent activity of a gastric-cancer cell line, MKN-1. This level was twice the highest activity in non-tumor chronic liver disease therefore, telomerase activity in all non-tumor liver samples was below this level. The telomerase-positive incidence exceeding this cut-off level was 73% (11/15) in well-differentiated HCC, 94% (16/17) in moderately differentiated HCC and 100% (5/5) in poorly differentiated HCC. Well-differentiated HCC showed low positivity by other diagnostic markers. 21% by AFP, 0% by PIVKA-II and 13% by angiography. The detection of telomerase activity may thus be a useful additional tool for precise and early diagnosis of small differentiated HCC, even when diagnosis is inconclusive by conventional techniques.
高分化肝细胞癌（HCC）的精确诊断有时很难确立。采用端粒重复序列扩增法（TRAP）检测了37个直径小于3 cm的HCC结节中的端粒酶活性，其中包括24个细针穿刺活检标本、22个非肿瘤性慢性肝病组织（9个慢性肝炎和13个肝硬化）以及3个正常肝组织。通过对样品进行系列稀释来检测端粒酶活性，并使用内部端粒酶检测标准品（ITAS）进行定量。在所有HCC以及22个非肿瘤性慢性肝病组织中的11个中检测到了端粒酶活性。正常肝样品未检测到端粒酶活性。对于其在HCC诊断中的实际应用，端粒酶活性的临界值暂定为在胃癌细胞系MKN - 1的10细胞当量活性下为0.6 μg肝蛋白/检测。该水平是非肿瘤性慢性肝病中最高活性的两倍，因此，所有非肿瘤性肝样品中的端粒酶活性均低于此水平。在高分化HCC中，超过此临界值的端粒酶阳性发生率为73%（11/15），在中分化HCC中为94%（16/17），在低分化HCC中为100%（5/5）。高分化HCC通过其他诊断标志物显示出低阳性率。甲胎蛋白（AFP）为21%，异常凝血酶原（PIVKA-II）为0%，血管造影为13%。因此，即使传统技术诊断不明确，端粒酶活性的检测对于小分化HCC的精确和早期诊断可能是一种有用的辅助工具。
