He Guo-Ping, Shui Qing-Lin, Huang Yan, Zhang Si-Zhong, Yu Hong
Department of Medical Genetics, West China Hospital, Sichuan University, PR China.
Ai Zheng. 2004 Sep;23(9):1041-6.
BACKGROUND & OBJECTIVE: Telomerase is a ribonucleoprotein enzyme, which plays an important role in cell immortalization and carcinogenesis. Recent studies on the association of telomerase activity with prognostic factors of breast cancer were controversial due to different methods. This study was to establish a feasible assay of quantitative detection of telomerase activity based on silver staining, and investigate possible association between telomerase activity and clinicopathological prognostic factors in primary breast cancer.
Highly sensitive silver-staining telomeric repeat amplification protocol assay (SS-TRAP) was used to quantify telomerase activity in 52 frozen human breast cancer samples and their adjacent breast tissues, 32 benign lesions, and 14 normal mammary gland lesions. The association between telomerase activity and clinicopathological data was analyzed.
Telomerase activity was detected in 47 of the 52 breast cancer samples (90.38%), and in 10 of the 32 benign lesions, whereas no activity was detected in 37 of 52 adjacent nonmalignant breast tissues, and all 14 normal mammary gland tissues. The telomerase activity levels were 36.91+/-15.35, 8.27+/-4.37, 14.10+/-5.28, 0 (unit: TPG) in breast cancer, adjacent tissue of cancer, benign lesion, and normal tissue, respectively. The difference of telomerase activity was significant between breast cancer and the other 3 groups by using ANVOA (all P< 0.01). A strong correlation was found between telomerase activity and pathological category, and differentiation degree by logistic regression analysis, i.e. with ongoing tumor progression, telomerase activity appeared to increase in primary breast cancer (P=0.003, and P=0.004). No correlation was seen between telomerase activity and disease course, age, and menopause status of patients (all P >0.05). Telomerase activity level of invasive non-special cancer was higher than that of invasive special cancer(P< 0.05). Telomerase activity level of moderately/poorly differentiated carcer was higher than that of highly differentiated cancer (P< 0.05), while no obvious difference was found between moderately and poorly differentiated cancer (P >0.05).
The activation of telomerase might occur early in breast cancer,and plays a critical role in carcinogenesis and tumor development. Telomerase may serve as a specific marker of early diagnosis and prognosis in mammary gland neoplasm.
端粒酶是一种核糖核蛋白酶,在细胞永生化和癌变过程中起重要作用。近期关于端粒酶活性与乳腺癌预后因素关系的研究因方法不同而存在争议。本研究旨在建立一种基于银染的端粒酶活性定量检测方法,并探讨原发性乳腺癌中端粒酶活性与临床病理预后因素之间的可能关联。
采用高灵敏度银染端粒重复序列扩增法(SS-TRAP)对52例人乳腺癌冷冻样本及其癌旁乳腺组织、32例良性病变和14例正常乳腺病变中的端粒酶活性进行定量检测。分析端粒酶活性与临床病理数据之间的关联。
52例乳腺癌样本中有47例(90.38%)检测到端粒酶活性,32例良性病变中有10例检测到端粒酶活性,52例癌旁非恶性乳腺组织中有37例未检测到端粒酶活性,14例正常乳腺组织均未检测到端粒酶活性。乳腺癌、癌旁组织、良性病变和正常组织的端粒酶活性水平分别为36.91±15.35、8.27±4.37、14.10±5.28、0(单位:TPG)。采用方差分析,乳腺癌与其他3组之间端粒酶活性差异有统计学意义(均P<0.01)。经逻辑回归分析,端粒酶活性与病理类型和分化程度密切相关,即原发性乳腺癌中端粒酶活性随肿瘤进展而升高(P=0.003,P=0.004)。端粒酶活性与患者病程、年龄和绝经状态均无相关性(均P>0.05)。浸润性非特殊癌的端粒酶活性水平高于浸润性特殊癌(P<0.05)。中/低分化癌的端粒酶活性水平高于高分化癌(P<0.05),而中分化癌与低分化癌之间差异无统计学意义(P>0.05)。
端粒酶的激活可能在乳腺癌早期发生,并在癌变和肿瘤发展中起关键作用。端粒酶可作为乳腺肿瘤早期诊断和预后的特异性标志物。