Endocrine Abstracts

Prediction of the biological behavior in non-functioning pituitary adenomas (NFPA) according to morphological criteria is highly inaccurate. Reliable prognostic molecular markers could be useful in providing guidance in NFPA post-surgical follow-up.

Aim: To identify differentially expressed genes between aggressive and non-aggressive NFPAs and to assess their prognostic value.

Methods: Samples analyzed were selected from a series of 60 NFPAs consecutively resected in our institution between 1998 and 2005 and kept frozen at −80 °C. Criteria for aggressive NFPA were invasion of surrounding structures or central nervous system at diagnosis (Hardy III/IV), recurrence and/or regrowth of post-surgical remnants. cDNA from pooled aggressive and non-aggressive NFPAs samples were labelled and hybridized on cDNA arrays (Superarray Bioscience), containing 192 genes related to invasiveness and angiogenesis, and normalized expression for each gene was calculated. Overexpression of selected genes was individually assessed by RT-PCR and its association to clinical parameters of agressiveness was analyzed.

Results: 61.6% adenomas were classified as aggressive, and 38.4% as non-aggressive NFPAs. The expression of a subset of genes was 1.5 to 3.9 fold higher in aggressive NFPAs; among them, growth factors and their receptors (KGF, HGF, PDGFa, TGFb1, TGFb3, FGFR2, FGFR3), chemokines (CXCL1, CXCL4), metalloproteases (Meth1, MMP9) and other proteins related to cellular adhesion and migration, such as osteopontin and cadherin-5, were identified. By RT-PCR, cadherin-5 was found to be expressed in 100% of aggressive-NFPAs but only in 8.7% of non-aggressive NFPAs. Moreover, a trend toward a higher expression of osteopontin in NFPAs invading cavernous sinus was found. Differences in CXCL4 expression were not individually detected.

Conclusions: cDNA arrays are useful to identify differentially expressed genes in NFPAs with discordant clinical behavior. Cadherin-5 and osteopontin are potential markers of aggressiveness in NFPAs, a fact that might be related to a pro-angiogenic and pro-invasive state.