Bhatia J K, Chaudhary Tripta, Boruah Dibyajyoti, Bharadwaj Reena
Senior Advisor & Head (Pathology), Command Hospital (Eastern Command), Kolkata, India.
Resident, Department of Pathology, Armed Forces Medical College, Pune, India.
Med J Armed Forces India. 2022 Jul;78(3):345-354. doi: 10.1016/j.mjafi.2021.10.013. Epub 2021 Dec 16.
Breast cancer is the leading cause of cancer-related deaths in Asia and is emerging as the commonest female malignancy. Angiogenesis or neovascularization is important for the growth and spread of malignant tumors, and quantitative assessment of angiogenesis may prove valuable in prognostication. This study was undertaken to quantify and explore angiogenesis with immunohistochemistry with CD 34, CD 105, and vascular endothelial growth factor (VEGF), as well as morphometric analysis and correlate with the grades of the invasive breast carcinoma.
Angiogenesis was assessed by morphometry and immunohistochemistry. Seventy cases of invasive ductal carcinoma (IDC) and twenty-five benign cases as controls were included in the study. Morphometry was performed on the CD34 and CD105 (Endoglin) stained representative histologic sections with the use of a computerized digital photomicrograph system using image analyzing software. Morphometric analysis and evaluation of vascular parameters, i.e. microvessel density (MVD), microvessel caliber (VC), and total microvessel boundary density (TVBD), were calculated. Semiquantitative assessment of angiogenesis of VEGF-stained sections was done by scoring. Immunohistochemical staining was correlated with the histological grade of the tumors. MVD, mean VC, TVBD with their mean values, SD, and range were calculated using Statistical Package for The Social Sciences (Version 20). One-way analysis of variance (ANOVA) with Tukey HSD was performed to assess the difference of the parameters for the groups. Spearman rank correlation coefficients ρ were calculated.
The vascular parameters were significantly more in malignant lesions as compared to benign lesions and showed differences with increasing grade. Grades of breast carcinoma showed a mild positive correlation with VEGF (ρ = 0.467), MVD-CD34 (ρ = 0.422) and VC-CD34 (ρ = 0.482); and moderate positive correlation with TVBD-CD34 (ρ = 0.615), VC-CD105 (ρ = 0.527), and TVBD-CD105 (ρ = 0.354). When these parameters were compared with each other for all four groups, VEGF showed a mild positive correlation with MVD-CD34 (ρ = 0.295), TVBD-CD34 (ρ = 0.339), and TVBD-CD105 ((ρ = 0.277). MVD-CD105 showed a mild positive correlation with MVD-CD34 TVBD-CD105 also showed a strong positive correlation with MVD-CD34. VC-CD105 showed a moderate positive correlation with VC-CD34. CD 105 stained fewer but larger caliber vessels.
In this study, vascular parameters showed significant differences in three grades of IDC with CD34. Differences were seen in vascular parameters stained with CD105 in three grades of IDC. Expression of VEGF also showed significant differences with positive correlations in the three grades of IDC. CD34 highlighted both old and newly formed microvessels. CD 105 stained fewer but larger caliber microvessels. VC-CD105 can be an extremely useful adjunct along with VEGF and CD34 to study angiogenesis of vessels in IDC.
乳腺癌是亚洲癌症相关死亡的主要原因，并且正成为最常见的女性恶性肿瘤。血管生成或新生血管形成对于恶性肿瘤的生长和扩散很重要，血管生成的定量评估可能在预后判断中具有重要价值。本研究旨在通过免疫组织化学方法检测CD 34、CD 105和血管内皮生长因子（VEGF）来量化和探索血管生成情况，同时进行形态计量分析，并将其与浸润性乳腺癌的分级相关联。
通过形态计量学和免疫组织化学评估血管生成情况。本研究纳入了70例浸润性导管癌（IDC）病例和25例作为对照的良性病例。使用计算机化数字显微图像系统及图像分析软件，对CD34和CD105（内皮糖蛋白）染色的代表性组织学切片进行形态计量分析。计算形态计量学分析及血管参数评估结果，即微血管密度（MVD）、微血管管径（VC）和总微血管边界密度（TVBD）。通过评分对VEGF染色切片的血管生成进行半定量评估。免疫组织化学染色结果与肿瘤的组织学分级相关联。使用社会科学统计软件包（版本20）计算MVD、平均VC、TVBD及其平均值、标准差和范围。采用带有Tukey HSD的单因素方差分析（ANOVA）来评估各组参数的差异。计算Spearman等级相关系数ρ。
与良性病变相比，恶性病变中的血管参数明显更多，并且随着分级增加而呈现差异。乳腺癌分级与VEGF（ρ = 0.467）、MVD - CD34（ρ = 0.422）和VC - CD34（ρ = 0.482）呈轻度正相关；与TVBD - CD34（ρ = 0.615）、VC - CD105（ρ = 0.527）和TVBD - CD105（ρ = 0.354）呈中度正相关。当对所有四组中的这些参数进行相互比较时，VEGF与MVD - CD34（ρ = 0.295）、TVBD - CD34（ρ = 0.339）和TVBD - CD105（ρ = 0.277）呈轻度正相关。MVD - CD105与MVD - CD34呈轻度正相关，TVBD - CD105与MVD - CD34也呈强正相关。VC - CD105与VC - CD34呈中度正相关。CD 105染色的血管数量较少但管径较大。
在本研究中，血管参数在三个等级的IDC中用CD34检测时显示出显著差异。在三个等级的IDC中，用CD105染色的血管参数也存在差异。VEGF的表达在三个等级的IDC中也显示出显著差异且呈正相关。CD34突出显示了新旧形成的微血管。CD 105染色的微血管数量较少但管径较大。VC - CD105与VEGF和CD34一起，可能是研究IDC中血管生成的极其有用的辅助指标。
