乳腺癌发生发展与肿瘤血管生成的相关性分析

Relevance of tumor angiogenesis in occurrence and development of breast cancer

目的探讨血管内皮生长因子（VEGF）与乳腺癌发生发展及血管生成之间的相关性。方法采用免疫组化染色法（SP法）分别检测88例乳腺浸润性导管癌、25例乳腺原位癌、15例乳腺不典型增生和100例乳腺良性病变患者术后标本中VEGF的表达水平及微血管密度（MVD）值。结果乳腺良性病变、乳腺不典型增生、乳腺原位癌和乳腺癌标本中VEGF阳性率分别为22．0％（22／100）、33．3％（5／15）、56．0％（14／25）和70．5％（62／88），乳腺良性病变组最低，乳腺癌组最高，4组VEGF表达水平呈依次升高趋势（P=0．000）；乳腺癌组中淋巴结转移阳性组VEGF表达水平高于未转移组（P=0．015），VEGF在Ⅱb期＋Ⅲ期组中表达水平高于Ⅰ期＋Ⅱa期组（P=0．006），C—erbB-2阳性组中VEGF表达水平高于阴性组（P=0．016），随着癌组织学分级的升高VEGF表达水平也呈逐渐升高趋势（P=0．017）；乳腺良性病变、乳腺不典型增生、乳腺原位癌和乳腺癌标本中MVD值（个）分别为14±4、18±4、20±6和23±15，良性病变组中MVD值最低，乳腺癌组中MVD值最高，4组MVD值呈逐步升高趋势（P=0．000），其中在乳腺癌组中发现随着癌组织学分级的升高MVD值也呈现出逐渐增加趋势（P=0．006）；在VEGF阳性组中MVD值高于VEGF阴性组（P=0．000），乳腺癌组中随着VEGF表达水平的升高MVD值也呈现出逐渐增加趋势（P=0．000）。结论VEGF在乳腺浸润性导管癌的肿瘤血管生成及转移过程中可能发挥重要的调控作用。VEGF和MVD值可作为反映乳腺癌生物学行为的指标之一。VEGF可能与乳腺癌的发生发展有关。以VEGF为靶点的抗血管生成治疗策略有望成为治疗C—erbB-2阳性患者的一条新的途径。

Objective To detect the differential expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） count in benign and malignant breast lesions to clarify the correlation of VEGF expression with the occurrence and progression of breast cancer and angiogenesis. Methods Immunohistochemistry （SP method） was used to examine the expression of VEGF and MVD count in 88 intra-operatively harvested samples of invasive ductal breast carcinoma, 25 samples of breast carcinoma in situ, 15 samples of atypical breast hyperplasia and 100 samples of benign breast lesions obtained. Results The positive rate of VEGF in invasive ductal breast carcinoma group was 70. 5% and it was significantly higher than those of benign breast lesions, atypical breast hyperplasia and breast carcinoma in situ groups （ 22. 0%, 33.3% and 56. 0% respectively, P = 0. 000）. The positive rate of VEGF with lymph node metastasis was higher than that without lymph node metastasis （ P = 0. 015 ）. The positive rate of VEGF in Stages Ⅱ b- Ⅲ was higher than that in Stages Ⅰ - Ⅱ a （ P = 0. 006）. The positive rate of VEGF in C-erbB-2 positive group was higher than that in C-erbB-2 negative group （ P = 0. 016 ） . An elevated expression of VEGF was observed as the tissue differentiation degree increased （ P = 0. 017 ）. The MVD value of invasive ductal breast carcinoma group was 23 ± 15 and it was significantly higher than those of benign breast lesions, atypical breast hyperplasia and breast carcinoma in situ groups （ 14 ± 4, 18 ±4 and 20 ± 6 respectively, P = 0. 000）. In invasive ductal breast carcinoma group, a significant higher MVD value was observed as the tissue differentiation degree increased （P =0. 006）. The MVD value in VEGF positive group was higher than that in VEGF negative group （P =0. 000）. In invasive ductal breast carcinoma, the MVD count increased significantly with the elevated expression of VEGF （ P = 0. 000 ）. Conclusion In invasive duetal breast carcinoma, angiogenesis and metastasis are mediated mainly by VEGF. The expressions of VEGF and MVD may be two of reference predictors for biological behaviors of breast carcinoma. The occurrence and progression of breast cancer might be correlated with the expression of VEGF. The VEGF-targeting antiangiogenic therapy is expected to become a new therapeutic modality for C- erbB-2 positive patients.