The Role of Mediators of Cell Invasiveness, Motility, and Migration in the Pathogenesis of Cavernous Sinus and Sphenoid Sinus Bone Invasion in Pituitary Adenomas

Background: This study aims to understand the molecular mechanisms governing growth and invasion patterns in pituitary adenoma (PA). We investigated the expression of factors known to regulate invasiveness, cell motility, and migration, and compared the data with clinical and radiological data for patterns of cavernous sinus invasion, sphenoid sinus bone invasion, and brain invasion.

Methods: We studied 100 PAs treated at our institution with sufficient radiological data and paraffin blocks to create a tissue microarray. We used a combination of real-time PCR and immunohistochemical analysis to quantify extent of expression of β1-integrin, osteopontin, and MMP-1.

Results: β1-integrin: All cases were positive for β1-integrin. No significant difference was present between invasive and non-invasive PAs. Extent of ß1-integrin expression was significantly different within subgroups (P < 0.05); mean extent of staining was higher in cavernous sinus invasive versus non-invasive adenomas. MMP-1: MMP-1 immunoreactivity was observed in 93% of PAs. Mean extent of staining is higher in invasive PA. Interestingly, similar correlation is observed with the FGFR4 expression levels and MMP-1 score of tumor groups. Osteopontin: Osteopontin immunoreactivity was observed in only 60% of Pas; however, all cavernous sinus invasive PAs were positive. Extent of osteopontin expression was significantly different between invasive and non-invasive PAs (P < 0.05); mean extent of staining was higher in invasive PA.

Conclusions: Osteopontin seems to play a major role in the cavernous sinus invasiveness of PAs, and a high MMP-1 score is characteristic of invasive PAs. Moreover, high FGFR4 levels of PAs seem to be responsible for the induction of MMP-1 expression in PAs.