Bcl-2蛋白 血管内皮生长因子在乳腺癌中的表达及其与预后相关性的研究

目的探讨凋亡抑制基因bcl-2蛋白及血管内皮生长因子(VEGF)表达在乳腺癌中的意义,及其与影响乳腺癌预后因素的相关性,探讨二者在细胞癌变过程中的作用及意义。方法应用免疫组织化学的方法,对64例随访5年以上的乳腺癌、19例良性乳腺组织、12例乳腺不典型增生的bcl-2蛋白、VEGF、雌激素受体(ER)、孕激素受体(PR)及C-erbB-2进行检测。结果64例乳腺癌组织中,bcl-2蛋白表达的总阳性率为65.6%(42/64),bcl-2高表达的病例,组织学分级高,易出现腋淋巴结转移;VEGF在乳腺癌组织中总的阳性表达率为62.5%(40/64),与肿瘤体积大、TNM分期晚、高组织学分级、腋淋巴结转移、ER阴性、C-erbB-2阳性等预示预后差等因素有显著相关性;乳腺癌中bcl-2与VEGF表达呈正相关(r=0.4172,P=0.0001)。在正常乳腺组织、乳腺不典型增生组织中bcl-2蛋白、VEGF表达的阳性率均低于乳腺癌组织,差异有显著性(P<0.01)。结论Bcl-2表达失调可导致乳腺癌细胞凋亡调控紊乱,bcl-2基因影响肿瘤的生物学行为;VEGF参与了乳腺癌的侵袭与转移调节,VEGF高表达常提示预后差;bcl-2基因可能通过调节细胞的凋亡而参与乳腺癌的发生发展;VEGF与bcl-2的表达呈正相关,VEGF是否能上调bcl-2蛋白有待进一步研究证实。

The expression of bcl-2,VEGF in breast cancer and the of relationship between bcl-2,VEGF and other prognostic factors

Objective To investigate the relationship between the expression of bcl-2,VEGF and other prognostic factors which significantly influence the survival rate after surgical resection of primary breast cancer.Meanwhile,the expression of bcl-2,VEGF,ER,PR,and C-erbB-2 of atypical hyperplasia and normal breast tissues are also to be studied.Methods Sixty-four women with primary breast carcinoma were studied for the expression of bcl-2 and VEGF proteins.The expression of ER,PR,C-erbB-2,bcl-2,and VEGF in nineteen benign breast tissues and twelve atypical hyperplasia breast tissues were also examined by automated immunohistochemical assay.Results Forty-two(65.6%) and forty (62.5%) breast cancer cases were found positive to bcl-2 and VEGF,respectively,as indicated by immunohistochemistry.A statistically significant association was found between expression of bcl-2 and high grade (grade Ⅲ) (P=0.009), positive lymph nodes (P=0.014), positivity of ER (P=0.010), positiveity of PR (P=0.010).The expression of VEGF was not related to menopausal status,but was negatively related to the estrogen receptor and.progesterone receptor (P<0.05),at same time,VEGF was positively related to tumor size (P=0.012), lymph nodes(P=0.004),highgrade (P=0.005),TNMⅢ (P=0.012),C-erbB-2 (P=0.001).Between bcl-2 and VEGF,there existed positive correlation (r=0.4172,P=0.0001).And there was a trend that from benign breast tissues to atypical hyperplastic breast tissues to breast carcinoma,the expression of bcl-2 and VEGF became higher and higher.This trend was statistically significant(P=0.001,0.002).Conclusion Disorder of bcl-2 expression may result in the disorder of apoptosis-modulation of breast cancer cell;bcl-2 gene influences the biological behavior of tumor.As a potent angiogenic factor,VEGF is associated with a poor prognosis of primary breast cancer.Bcl-2 regulates the progession of cell apoptosis from benign breast tissues to atypical hyperplastic breast tissues to breast carcinoma,and influences the biological behavior of breast tumor cells.VEGF correlates positively with bcl-2 expression;whether it up-regulates bcl-1 protein is still pending further verification.