Integrins αvβ3 and αvβ5 as prognostic, diagnostic, and therapeutic targets in gastric cancer

We investigated the expression of two alpha(v) integrins, alpha(v)beta(3) and alpha(v)beta(5), in gastric cancer (GC) by testing the following hypotheses: that these molecules are expressed in GC; that they are implicated in GC biology; that they help to distinguish between the two major histological subtypes of GC, according to Laur,n; and that they are prognostically relevant. Formalin-fixed and paraffin-embedded tissue samples from 482 GC samples were stained immunohistochemically using rabbit monoclonal antibodies directed against alpha(v)beta(3) (EM22703) and alpha(v)beta(5) (EM09902). Immunostaining of tumor, stroma, and endothelial cells was evaluated separately by the quantity and intensity, generating an immunoreactivity score. The immunoreactivity score of both antibodies was correlated with clinicopathology data and patient survival. Each integrin was expressed in at least one tumor component in all GCs. Both were expressed significantly more often in the intestinal phenotype according to Laur,n. Moreover, patients who grouped as positive for expression of alpha(v)beta(3) on endothelial cells, and patients with an intestinal type GC, grouped as negative for expression of alpha(v)beta(5) on stroma cells, had significantly longer survival. The expression of alpha(v)beta(5) on stroma cells was confirmed to be an independent prognostic factor of intestinal-type GC. The expression of alpha(v)beta(3) and alpha(v)beta(5) in at least one tumor component in all GC samples is an interesting new result that should form a basis for further investigations; for example, regarding selective integrin antagonists and the value of alpha(v)beta(3) and alpha(v)beta(5) as putative prognostic biomarkers. Moreover, both markers might be helpful in the routine classification of GC subtypes.