A strong inverse relationship between elevated IGFBP-2 levels and low p16INK4a indicates a negative regulatory function of p16INK4a for IGFBP-2 (98) similar to the negative correlation of IGFBP-2 mRNA and PTEN expression levels found both in glioblastomas and prostate cancers, implicating IGFBP-2 as a biomarker for PTEN status (95). This evidence concerns the gene PTEN and Familial prostate cancer.