Angioarchitectural morphometrics of brain tumors: are there any potential histopathological biomarkers?

Normal brain parenchyma has a highly complex microvascular structure that undergoes re-modelling in the presence of a tumor. A detailed understanding of the clinical and pathological aspects of neo-angiogenesis in malignant human brain tumors is essential in order to ensure the successful clinical application of anti-angiogenic therapy. As the quantification of various aspects of tumor vasculature may provide an indication of angiogenic activity, it is reasonable to assume that identifying specific new biomarkers will help investigators to design more appropriate and less toxic anti-angiogenic treatment strategies. Research into the quantitative analysis of microangioarchitectures can be divided into two main branches: morphometrics and biomarker research. Morphometrics adds quantitative elements to the qualitative description of tissues by means of Euclidean and fractal geometrical parameters, whereas biomarker research seeks predictors that can be used in clinical applications. All of the many morphometric parameters used to analyze microvascular networks in brain tumors have their pros and cons, but none has yet been validated as a reliable biomarker. This review describes the helpfulness and limitations of the morphometric parameters that have so far been proposed, and the current "state-of-the-art" in planning future research into biomarkers and morphometry of the microangioarchitecture of brain tumors. It concludes by discussing the need to make a multiparametric analysis of histological specimens that can be integrated with qualitative and quantitative analyses based on neuroradiological and nuclear medicine techniques in order to provide a valid holistic representation of brain tumors. An empirical algorithm for assessing the microangioarchitecture of brain tumors is also provided.