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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.

Conclusion

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.

SUBMITTER: Boger C 

PROVIDER: S-EPMC4572058 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Böger Christine C   Warneke Viktoria S VS   Behrens Hans-Michael HM   Kalthoff Holger H   Goodman Simon L SL   Becker Thomas T   Röcken Christoph C  

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20141015 4


<h4>Background</h4>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.<h4>Methods</h4>Formalin-fixed and paraffin-embedded tissue samples from 482 GC samples were stained immunohistochemically using  ...[more]

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