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人乳腺浸润性导管癌中血管生成标志物表达的形态计量学和免疫组织化学研究

Morphometric and immunohistochemical study of angiogenic marker expressions in invasive ductal carcinoma of human breast.

作者信息

Safwat M D, Habib F, Elayat A, Oweiss N, Reffat S, Algaidi S

机构信息

Faculty of Medicine Anatomy, AL-Madinah Al-Monwarah, Saudi Arabia.

出版信息

Folia Morphol (Warsz). 2009 Aug;68(3):144-55.

Abstract

Breast cancer is the leading cause of cancer deaths among women. Results from experimental studies suggest that tumour progression and metastasis in breast cancer are angiogenesis dependant. The College of American Pathologists has stated that further study of quantification of tumour angiogenesis is still required to demonstrate its prognostic value in breast cancer. In this study, not only the microvascular density (MVD), but also the vascular area ratio (VAR), and the vascular count in different grades of invasive ductal breast carcinoma were assessed using a pan-endothelial marker, CD34, and monoclonal antibody to CD105, by employing computer assisted morphometric measurements. In addition, quantitative expression of vascular endothelial growth factor (VEGF) was detected. Correlation of the vascular parameters and VEGF expression with the different grades of invasive ductal breast carcinoma was clarified. Immunohistochemical staining for the CD105, CD34, and VEGF antibodies were performed in 25 patients with invasive ductal carcinoma in King Fahd Hospital, Saudi Arabia. Normal breast tissue samples comprised 15 specimens detected at the safety margin of the malignant breast cases were collected. Positive CD34 stained blood-vessel endothelial cells were observed in all normal breast tissues. In contrast, CD105 and VEGF expression were not expressed in the normal breast ducts and lobules. Widespread staining for CD34, to a lesser extent CD105, and VEGF expression were seen in all tumour specimens with different grades. Significant differences in the vascular parameters, stained with antiCD34, were observed between normal breast tissues and invasive ductal carcinoma. In addition, the vascular parameters stained with antiCD34 and antiCD105, and the percentage of VEGF expression in the three grades of invasive ductal carcinomas showed significant differences with positive correlations. In conclusion, MVD as well as VAR are considered to reflect the final result of the tumour angiogenesis cascade. In addition, VEGF expression was found to be a useful angiogenic marker. However, few cases were VEGF negatively stained. Thus, the expression of MVD, VAR, and to a lesser extent VEGF might be reference predictors for the biological behaviour and prognosis of breast carcinoma.

摘要

乳腺癌是女性癌症死亡的主要原因。实验研究结果表明,乳腺癌的肿瘤进展和转移依赖于血管生成。美国病理学家学会指出,仍需进一步研究肿瘤血管生成的量化,以证明其在乳腺癌中的预后价值。在本研究中,通过计算机辅助形态测量,使用全内皮标志物CD34和抗CD105单克隆抗体,不仅评估了微血管密度(MVD),还评估了血管面积比(VAR)以及不同分级的浸润性导管癌中的血管计数。此外,检测了血管内皮生长因子(VEGF)的定量表达。阐明了血管参数和VEGF表达与不同分级浸润性导管癌的相关性。在沙特阿拉伯法赫德国王医院对25例浸润性导管癌患者进行了CD105、CD34和VEGF抗体的免疫组织化学染色。正常乳腺组织样本包括在恶性乳腺病例安全边缘处检测的15个标本。在所有正常乳腺组织中均观察到CD34染色阳性的血管内皮细胞。相反,正常乳腺导管和小叶中未表达CD105和VEGF。在所有不同分级的肿瘤标本中均可见CD34的广泛染色,CD105染色程度较轻,且有VEGF表达。正常乳腺组织与浸润性导管癌之间,抗CD34染色的血管参数存在显著差异。此外,抗CD34和抗CD105染色的血管参数以及三级浸润性导管癌中VEGF表达的百分比显示出显著差异且呈正相关。总之,MVD以及VAR被认为反映了肿瘤血管生成级联反应的最终结果。此外,发现VEGF表达是一种有用的血管生成标志物。然而,很少有病例VEGF染色阴性。因此,MVD、VAR的表达以及程度较轻的VEGF表达可能是乳腺癌生物学行为和预后的参考预测指标。

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