Abstract
BackgroundWe investigated the expression of two αv integrins, αvβ3 and αvβ5, 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.MethodsFormalin-fixed and paraffin-embedded tissue samples from 482 GC samples were stained immunohistochemically using rabbit monoclonal antibodies directed against αvβ3 (EM22703) and αvβ5 (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.ResultsEach 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 αvβ3 on endothelial cells, and patients with an intestinal type GC, grouped as “negative” for expression of αvβ5 on stroma cells, had significantly longer survival. The expression of αvβ5 on stroma cells was confirmed to be an independent prognostic factor of intestinal-type GC.ConclusionThe expression of αvβ3 and αvβ5 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 αvβ3 and αvβ5 as putative prognostic biomarkers. Moreover, both markers might be helpful in the routine classification of GC subtypes.Electronic supplementary materialThe online version of this article (doi:10.1007/s10120-014-0435-2) contains supplementary material, which is available to authorized users.
Highlights
In recent decades we have witnessed major advances in the understanding of the epidemiology, pathology, and pathogenesis of gastric cancer (GC)
Background We investigated the expression of two av integrins, avb3 and avb5, 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 Lauren; 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 avb3 (EM22703) and avb5 (EM09902)
Summary
In recent decades we have witnessed major advances in the understanding of the epidemiology, pathology, and pathogenesis of gastric cancer (GC). The two major histological subtypes of GC according to Lauren, diffuse-type and intestinal-type GC, have distinct tumor dissemination patterns and show diverse pathogeneses and expression profiles, likely resulting from molecular differences in tumor epithelial and stroma cells [4, 5]. The distinction between diffuse and intestinal subtype in GC has prognostic significance, it is still widely neglected in patient-tailored treatment of GC [6, 7]. We investigated the expression of two av integrins, avb and avb, 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 Lauren; and that they are prognostically relevant.
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