Quantitative analysis of vessels with smooth muscle layer in astrocytic tumors: correlation with histological grade and prognostic significance

Abstract

Angiogenesis plays an important role in the progression of astrocytic tumors and its evaluation is a major prognostic factor. Although the form of proliferating vessels ranges from fine capillaries to welldeveloped vascular structures with a smooth muscle layer, the characteristics of vascular smooth muscle cells (SMCs) are not understood in detail. We therefore examined the density, size and shape of tumor vessels, as well as CD34-immunoreactive (CD34-Vs) or α-smooth muscle actin-immunoreactive (SMA-Vs) vessels in 46 primary astrocytomas (grade II diffuse astrocytomas, n=11, grade III anaplastic astrocytomas, n=15, grade IV glioblastomas, n=20) and in normal brain tissues from 10 autopsies. We also examined the expression of high molecular weight caldesmon (h-CD, a marker of the contractile phenotype of smooth muscle) and of plateletderived growth factor receptor ß (PDGFR-ß). The SMAVs were significantly more dense and larger in grade IV than grade III, whereas those of CD34-Vs did not differ between grade III and IV. Changes in the shape of CD34-Vs and SMA-Vs correlated with histological grading. The expression of h-CD was reduced, whereas that of PFGFR-ß was increased in high gradeastrocytomas. Kaplan-Meier analysis indicated that the density of SMA-Vs, the size of both CD34 and SMA-Vs and PDGFR-ß expression were significant prognostic factors. These findings suggest that SMA-Vs are significantly associated with the progression of astrocytomas and that these vessels provide useful information for the histological diagnosis and survival of patients with these types of brain tumors