Towards an integrated molecular and clinical strategy to predict early recurrence in surgically resected...

Pituitary adenomas (PA) are histologically benign tumors of the sella that are capable of recurrence following resection. No mechanism exists to predict accurately the risk of recurrence in patients with PA following successful gross total surgical resection. We used microarray-based gene expression profiling to search for genotypically distinct subgroups of non-functional PA associated with the early recurrent phenotype. Rigorous phenotypic controls were used to select four patients with PA with early (<12 months) recurrence and seven patients with non-recurrent PA for comparative molecular analysis. Seventy genes with differential expression patterns between the phenotypic groups were identified, although this required some relaxation of rigid multiple-testing corrections. While some of these genes may therefore represent statistical false discoveries attributable to limited sample size, the CHL1 gene has a differential expression patterns that suggests a potential role as a predictor of recurrence phenotype. Transcriptome-level differences between early recurrent and non-recurrent non-functional PA appear to be subtle, although CHL1 expression may be a candidate for further study as a class discriminator. This suggests two possibilities with regard to recurrence; (i) that microscopic residual disease unidentifiable either by the surgeon or by current neuroimaging strategies may serve as a focus for early recurrence or that biological differences in recurrence phenotypes may occur outside of the transcriptome. These findings are useful for focusing future investigations into the clinical and biological mechanisms of PA recurrence as well as for development of strategies designed to predict prospectively these recurrence phenotypes.