乳腺癌中干细胞标志物ALDH1及VHL/HIF-1α的表达及意义

Expression of cancer stem cell marker ALDH1 and VHL /HIF-1α and their impact on the prognosis of breast cancer

目的探讨乙醛脱氢酶1(acetaldehyde dehydrogenase 1,ALDH1)、缺氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)及希佩尔林道(Von Hippel-Lindau,VHL)在乳腺癌中表达的关系及意义。方法采用免疫组化SP法分别检测15例乳腺正常组织、30例乳腺增生组织及40例乳腺浸润性导管癌组织中干细胞标志物ALDH1、HIF-1α及VHL的表达。结果 (1)AL-DH1、HIF-1α及VHL在乳腺正常组织、乳腺增生组织、乳腺浸润性导管癌组织中阳性率差异有统计学意义(P<0.05)。(2)Spearman等级相关分析显示VHL与HIF-1α、肿瘤病理分级、临床分期、肿块大小、淋巴结转移呈负相关;HIF-1α与肿瘤病理分级、临床分期、肿块大小、淋巴结转移呈正相关(P<0.05)。(3)HIF-1α与ALDH1在乳腺癌中的表达有相关性(r=0.976,P=0.001),VHL与ALDH1在乳腺癌中的表达有相关性(r=0.971,P=0.001)。结论乳腺癌中存在ALDH1、HIF-1α、VHL的异常表达,三者在乳腺癌发生、发展、侵袭和转移中可能具有重要作用。VHL/HIF-1α信号通路可能与肿瘤干细胞生长和分化密切相关。

Purpose To investigate the ALDH1, HIF-1α and VHL expression and their impact on the prognosis of patients with breast cancer. Methods Immunohistochemistry （SP method） was used to detect the stem cell marker ALDH1 ,VHL and HIF-1α expression in 15 cases of normal breast tissue, 30 cases of breast hyperplasia and 40 cases of breast invasive ductal carcinoma. Results Positive expression rate of ALDHI HIF-1α and VHL among normal tissue, breast hyperplasia, and breast invasive ductal carcinoma was statisti- cally significant （P 〈 0. 05 ）. Spearman rank correlation analysis showed that the VHL and HIF-1α, tumor grade, clinical stage, tumor size, lymph node metastasis were negatively correlated, in which HIF-1α and tumor grade, clinical stage, tumor size, lymph node me- tastasis were positively correlated （P 〈 0. 05）. In addition, the expression of HIF-lct and VHL was associated with ALDH1 in breast cancer （r = 0. 976, P = 0. 001 ; r = O. 971, P = O. 001 ; respectively）. Conclusion Abnormal expression of ALDH1, HIF-1α and VHL exists in breast cancer, which suggests that they may play an important role in the progression, invasion and metastasis. VHL/ HIF-1α signaling pathway may be related to cancer stem cell growth and differentiation.