乳腺癌组织中端粒酶活性的定量检测及其与临床病理的关系

背景与目的:端粒酶是一种在细胞永生化及癌症发生过程中起重要作用的核蛋白酶。最近关于乳腺癌中端粒酶活性与预后因素间的关系,因研究方法的差异而呈现出不一致的报道。本研究旨在建立一种可行的银染端粒酶定量检测法,以探讨乳腺癌中端粒酶活性与临床病理学预后因素间的关系。方法:运用银染端粒重复序列扩增法(SS-TRAP)检测了52例新鲜乳腺癌及其癌旁组织,32例乳腺良性病变和14例正常乳腺组织中端粒酶的活性表达,对结果予以定量并结合临床资料进行分析。结果:乳腺癌、癌旁组织、良性病变及正常乳腺组织中端粒酶阳性率分别为90.38%(47/52)、28.85%(15/52)、31.25%(10/32)、0(0/14)。端粒酶分别为36.91±15.35、8.27±4.37、14.10±5.28、0(TPG单位),单因素方差分析结果显示,乳腺癌组端粒酶活性水平明显高于其他3组(P值均<0.01)。Logistic回归分析结果表明,乳腺癌中端粒酶的表达与病理类型、分化程度明显相关(P=0.003及0.004),即随着肿瘤的进展,端粒酶活性亦增加。其中,浸润性非特殊癌端粒酶活性水平明显高于浸润性特殊癌(P<0.05);中、低分化癌端粒酶活性均高于高分化癌(P<0.05),中、低分化癌间无显著性差异(P>0.05)。端粒酶活性表达在患者病程、年龄、绝经状况间均无显著性差异(P>0.05)。结论:与经典TRAP

Quantitative detection of telomerase activity and its association with clinicopathological characteristics in breast cancer

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. METHODS: 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. RESULTS: 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). CONCLUSIONS: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.