Hyperplasia of Pericytes Is One of the Main Characteristics of Microvascular Architecture in Malignant Glioma

Abstract

Objectives

To investigate the role of pericytes in constructing the malformed microvessels (MVs) and participating microvascular architecture heterogeneity of glioma.

Methods

Forty human glioma tissue samples (WHO grade II-IV) were included in present study. Observation of blood vessel patterns, quantitative analysis of endothelial cells (ECs)- and pericyte-labeled MVs and comparison between malignant grades based on single- or double-immunohistochemical staining. The MV number density (MVND), microvascular pericyte number density (MPND), and microvascular pericyte area density (MPAD) were calculated. The expression of PDGFβ was also scored after immunostaining.

Results

In grade II glioma, most of tumor MVs were the thin-wall CD34 ⁺ vessels with near normal morphology. In addition to thin-wall CD34 ⁺ MVs, more thick-wall MVs were found in grade III glioma, which often showed α-SMA positive. Most of MVs in grade IV glioma were in the form of plexus, curled cell cords and glomeruloid microvascular proliferation while the α-SMA ⁺ cells were the main components. The MVs usually showed disordered arrangement, loose connection and active cell proliferation as shown by Ki67 and α-SMA coexpression. With the increase of glioma grades, the α-SMA ⁺ MVND, CD34 ⁺ MVND and MPND were significantly augmented although the increase of CD34 ⁺ MVND but not MPAD was statistically insignificant between grade III and IV. It was interesting that some vessel-like structures only consist of α-SMA ⁺ cells, assuming the guiding role of pericytes in angiogenesis. The expression level of PDGFβ was upregulated and directly correlated with the MPND in different glioma grades.

Conclusion

Hyperplasia of pericytes was one of the significant characteristics of malignant glioma and locally proliferated pericytes were the main constituent of MVs in high grade glioma. The pathological characteristics of pericytes could be used as indexes of malignant grades of glioma.