Integrins α(v)β(3) and α(v)β(5) as prognostic, diagnostic, and therapeutic targets in gastric cancer

BACKGROUND: We investigated the expression of two α(v) integrins, α(v)β(3) and α(v)β(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 Laurén; and that they are prognostically relevant. METHODS: Formalin-fixed and paraffin-embedded tissue samples from 482 GC samples were stained immunohistochemically using rabbit monoclonal antibodies directed against α(v)β(3) (EM22703) and α(v)β(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. RESULTS: 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 Laurén. Moreover, patients who grouped as “positive” for expression of α(v)β(3) on endothelial cells, and patients with an intestinal type GC, grouped as “negative” for expression of α(v)β(5) on stroma cells, had significantly longer survival. The expression of α(v)β(5) on stroma cells was confirmed to be an independent prognostic factor of intestinal-type GC. CONCLUSION: The expression of α(v)β(3) and α(v)β(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 α(v)β(3) and α(v)β(5) as putative prognostic biomarkers. Moreover, both markers might be helpful in the routine classification of GC subtypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10120-014-0435-2) contains supplementary material, which is available to authorized users.