Assessment of microvascular patterns and density in glioblastoma and their correlation with matrix metalloproteinase-9, p53, glial fibrillary acidic protein, and Ki-67

Abstract

Background and Aim: Microvascular patterns (MVPs) and microvessel density (MVD) can influence the progression of glioblastomas. This study aims to study MVP and MVD using immunohistochemistry, and examine any correlation with the expression of matrix metalloproteinase-9 (MMP-9), p53, glial fibrillary acidic protein (GFAP), and Ki-67 labeling index (Ki-67 LI) in 24 cases of glioblastoma multiforme. Materials and Methods: MVPs and MVD were studied by a dual staining method using periodic acid–Schiff stain with CD34 (MVDCD34), CD31 (MVDCD31), von Willebrand factor (MVDvWF), and factor VIII (MVDFVIII). The expression of MMP-9, p53, GFAP, and Ki-67 LI was analyzed using immunohistochemistry. The Pearson coefficient of correlation and intraclass correlation were obtained using SPSS software. Results: Five distinct categories of MVP were found: Microvascular sprouting (MS)/simple vessels, vascular clusters (VCs), vascular garlands, glomeruloid tufts, and vasculogenic mimicry. Of the MVPs, MS was the most common pattern and was present in all cases. On calculating the Pearson's correlation coefficient, different MVPs gave varying results regarding their correlation with MMP-9, p53, GFAP, and Ki-67 LI. MSCD34, CD31, vWF showed significant correlation with MMP-9 and Ki-67 LI, while MSFVIII did not show any correlation with Ki-67 LI. Only VCCD34 had a correlation with Ki-67 LI. No correlation between any of the MVPs and GFAP and p53 was appreciated. MVD ranged from: CD34 (9.2–41.9/hpf), FVIII (6.05–40.5/hpf), CD31 (5.1–40.7/hpf), and vWF (8.7–35.5/hpf). MVDCD34 and MVDCD31 correlated with MMP-9 and Ki-67, whereas, MVDvWF and MVD FVIII correlated with MMP-9. Interobserver agreement was seen only in the assessment of MVD and the MS type of MVP. Conclusion: MVD and MVPs had correlation with MMP-9, p53, GFAP, and Ki-67. These results could impact the development of strategies using antiangiogenic therapies.