title: Integrins αvβ3 and αvβ5 as prognostic, diagnostic, and therapeutic targets in gastric cancer.
abstract: BACKGROUND
  We 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.
  
  
  METHODS
  Formalin-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.
  
  
  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 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Pathology, Christian Albrechts University, Arnold-Heller-Str. 3, Haus 14, 24105, Kiel, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Böger
authors.affiliation: Department of Pathology, Christian Albrechts University, Arnold-Heller-Str. 3, Haus 14, 24105, Kiel, Germany.
authors.forename: Viktoria S
authors.initials: VS
authors.lastname: Warneke
authors.affiliation: Department of Pathology, Christian Albrechts University, Arnold-Heller-Str. 3, Haus 14, 24105, Kiel, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Behrens
authors.affiliation: Department of Experimental Cancer Research, Christian Albrechts University, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.affiliation: Oncology Platform, Department of Translational and Biomarkers Research, Merck KGaA, Darmstadt, Germany.
authors.forename: Simon L
authors.initials: SL
authors.lastname: Goodman
authors.affiliation: Department of General Surgery and Thoracic Surgery, Christian Albrechts University, Kiel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.affiliation: Department of Pathology, Christian Albrechts University, Arnold-Heller-Str. 3, Haus 14, 24105, Kiel, Germany. christoph.roecken@uksh.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019030:Receptors, Vitronectin / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D039302:Integrin alphaVbeta3; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5
keywords: Gastric cancer; Immunohistochemistry; Integrins; αvβ3; αvβ5