Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma

The PTEN tumor suppressor gene encodes a dual-specificity protein phosphata se that may play a key role in modulating integrin-mediated signals. Inacti vation of the PTEN gene has been detected in a small percentage of clinical ly localized prostate cancers but is common in metastatic disease. It has b een shown in glioblastoma cell lines that loss of chromosome 10q, where the PTEN gem is located, is associated with increased angiogenic activity in t he conditioned medium attributable to downregulation of thrombospondin-l, a negative regulator of angiogenesis. Therefore, we wished to determine whet her inactivation of PTEN might be associated with increased angiogenesis in prostate cancers, because increased angiogenesis in localized cancers is a ssociated with development of metastatic disease. Angiogenesis was assessed by counting microvessels in areas of maximal neovascularization after immu nostaining with anti-factor VIII-related antigen antibodies in eight cases with proven homozygous deletion of the PTEN gene and 24 control cases. Ther e was: a statistically significant correlation between PTEN inactivation an d increased microvessel counts. The microvessel density was higher at all G leason scores in the cases with PTEN inactivation compared with control cas es with the same score. To determine whether the increased angiogenesis in cases with PTEN inactivation was caused by downregulation of expression of the angiogenesis inhibitor thrombospondin-l, we analyzed a subset of the ca ses by immunostaining with anti-thrombospondin-1 antibody. Approximately 25 % of cases showed decreased staining of prostate cancer cells, but there wa s no correlation with PTEN inactivation. Thus, PTEN inactivation is associa ted with increased angiogenesis, but the increased, angiogenesis is not att ributable to downregulation of thrombospondin-1 expression. Copyright (C) 1 999 by W.B. Saunders Company.