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Integrins and their ligands are expressed in non-small cell lung cancer but not correlated with parameters of disease progression

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Abstract

The aim of this study was to investigate the expression of integrins, their ligands, and integrin signaling-related molecules in a cohort of human primary non-small cell lung cancers (NSCLC). Formalin-fixed and paraffin-embedded tissue samples from 215 NSCLC were immunohistochemically stained using antibodies directed against αvβ3, αvβ5, αvβ6, αvβ8, αv, osteopontin, fibronectin, vitronectin, epidermal growth factor (EGFR), vascular endothelial growth factor receptor (VEGFR), and Ki67. Immunostaining of tumor, stroma, and endothelial cells was evaluated separately by quantity and intensity (tumor cells) or intensity (stroma and endothelial cells) expressed in an immunoreactivity score. We studied correlations between the staining patterns of the different markers and of marker expression with clinicopathological data and patient survival. In the majority of NSCLC, each marker was expressed in at least one tumor component. As expected, αv and αv integrin heterodimers were significantly co-expressed, as were integrins and EGFR. Vitronectin was expressed significantly more often in smaller (T-category) and in well-differentiated tumors; Ki67 index was higher in larger (T-category) and in poorly differentiated tumors. No significant correlation was found between any marker expression and gender, venous invasion, lymph vessel invasion, lymph node metastasis, or survival. Although integrin expression does not seem to be associated with indicators of progression of NSCLC, the expression of αvβ3 in 89 % and αvβ5 in 100 % of NSCLC is novel and merits to be further investigated.

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Acknowledgments

We wish to thank Marten Rönckendorf for his excellent technical assistance and Christian Röder for the provision of follow-up data.

Conflict of interest

Simon L. Goodman is gainfully employed by Merck KGaA. All other authors declare that they have no conflict of interest. This work was supported by grants from Merck KGaA Germany.

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Authors and Affiliations

  1. Department of Pathology, Christian-Albrechts-University, Arnold-Heller-Str. 3, Haus 14, 24105, Kiel, Germany

    Christine Böger, Hans-Michael Behrens & Christoph Röcken

  2. Department of Experimental Cancer Research, Christian-Albrechts-University, Kiel, Germany

    Holger Kalthoff

  3. Translational Innovation Platform, Oncology, Merck KGaA, Darmstadt, Germany

    Simon L. Goodman

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  1. Christine Böger
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  2. Holger Kalthoff
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Correspondence to Christoph Röcken.

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Böger, C., Kalthoff, H., Goodman, S.L. et al. Integrins and their ligands are expressed in non-small cell lung cancer but not correlated with parameters of disease progression. Virchows Arch 464, 69–78 (2014). https://doi.org/10.1007/s00428-013-1506-1

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