Two Distinct Types Of Blood Vessels In Clear Cell Renal Cell Carcinoma Have Contrasting Prognostic Implications

Controversy surrounds the prognostic significance of microvessel density (MVD) in renal cell carcinoma (RCC), where both positive and negative correlations with outcome have been reported. Here, Yao and colleagues examine MVD as a prognostic marker in RCC, but also characterize the intratumoral blood vessels as “differentiated” or “undifferentiated”, based on CD31 and CD34 expression, to further elucidate the importance of tumor angiogenesis in the process of RCC progression.

The authors examined CD31, CD34, and CD105 expression in a tissue microarray generated from 78 patients with clear cell RCC. Of these, 53 had relapsed following surgery. “Undifferentiated” blood vessels were characterized as CD31+/CD34-. “Differentiated” blood vessels were characterized as CD34+ and were also noted to be surrounded by pericytes. Conventional tissue sectioning and immunohistochemistry was also done to validate the use of the tissue microarray in these experiments. The authors found that there was an inverse relationship between the percentage of differentiated and undifferentiated blood vessels in a given tumor and that elevated levels of undifferentiated vessels in the MVD correlated with increased tumor grade (p<0.0001) and a worse survival. In their multivariate analysis, an increased percentage of undifferentiated vessels contributing to the MVD was an independent predictor of poor outcome for patients with RCC (p=0.04).Angiogenesis features prominently in the biology of RCC progression and is also an attractive target for therapeutic intervention. This study demonstrates that not all blood vessels in a tumor are alike, and that an increased percentage of undifferentiated blood vessels (CD31+/CD34-, lacking pericytes) predicts a more aggressive phenotype and a worse outcome.(Source: Clinical Cancer Research : May 2007.)