Techniques to assess the proliferative potential of brain tumors

Assessment of brain tumor proliferative potential provides important prognostic information that supplements standard histopathologic grading. Many laboratories rely on mitotic figures to quantify the proliferative potential of brain tumors, but this conventional cellular proliferative index is subject to inter-observer variability and not consistently predictive for low-and high-grade tumors. Recent advancements in technology have made it possible to use proliferative indices as a standard supplement in pathology laboratories. Non-invasive tumor tissue measurements of cell proliferation can be performed using: bromodeoxyuridine labeling index (BrdU LI), flow cytometry (FCM), MIB-1 antibody to the Ki-67 antigen (MIB-1), proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar organizing regions (AgNOR). Each of these assays has been described in the literature with respect to its ability to predict tumor grade or outcome. At the present time MIB-1 and AgNOR are the simplest and most reliable of these techniques. In addition, advances in our understanding of the genetic alterations associated with proliferation promise to provide more specific markers of proliferative potential. Beyond the pathology laboratory, radiographic studies such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and most recently magnetic resonance spectroscopy (MRS) have been used as follow-up measures, assessing response to treatment and tumor recurrence, rather than as predictors of response to treatment. These radiographic tools, however, have the potential to provide an assessment of tumor proliferation without the need for invasive measures. In this article, we present a review of the current techniques utilized to understand the proliferative potential of brain tumors.