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Submaxillary gland androgen-regulated protein 3A expression is an unfavorable risk factor for the survival of oropharyngeal squamous cell carcinoma patients after surgery

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Abstract

Recently, increased expression of the submaxillary gland androgen-regulated protein 3A (SMR3A) was found in recurrent tumors of an orthotopic floor-of-mouth mouse tumor model after surgery. However, SMR3A expression in the pathogenesis of human malignancy and its correlation with the clinical outcome have not been addressed so far. We analyzed tissue microarrays with specimens from oropharyngeal squamous cell carcinoma (OPSCC) patients (n = 157) by immunohistochemistry and compared SMR3A expression with clinical and pathological features by statistical analysis. Strong SMR3A expression was found in almost 36 % of all primary OPSCCs. Although, SMR3A protein levels were not associated with any clinical or histopathological feature tested, univariate Kaplan–Meier analysis revealed a significant correlation between high SMR3A protein expression and poor progression-free (p = 0.02) and overall survival (p = 0.03). Furthermore, high SMR3A expression was an independent marker for poor clinical outcome [HR (SMR3Ahigh vs. SMR3low) = 2.32; 95 % CI = 1.03–5.23] concerning overall survival in a multivariate analysis of OPSCC patients with surgery as primary therapy (n = 100). Our data demonstrate for the first time increased SMR3A protein expression in the pathogenesis of OPSCC, which serves as an unfavorable risk factor for patient survival.

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Acknowledgments

We gratefully acknowledge Nataly Henfling, Ines Kaden and Antje Schuhmann for excellent technical assistance, and Michael Pawlita, Franz X. Bosch, Efterpie Kostareli, Pilar Bayo Zaera and Regina Mark for helpful discussion and critical reading of the manuscript. We thank the tissue bank of the National Center for Tumor Disease (Institute of Pathology, University Hospital Heidelberg) for providing paraffin-embedded tumor specimens of HNSCC patients. This work was supported by the Deutsche Forschungsgemeinschaft (PhD grant of the Graduiertenkolleg 793 to D.H., and HE5760/1-1 to J.H.), the Dietmar Hopp Stiftung (to D.H., P.K.P, and J.H.), and the Stiftung Tumorforschung Kopf-Hals (to J.H.).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Experimental Head and Neck Oncology, Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Jennifer Koffler, Gustavo Acuña Sanhueza, Karim Zaoui, Peter K. Plinkert & Jochen Hess

  2. Division of Genome Modifications and Carcinogenesis (F020), Infection and Cancer Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Dana Holzinger

  3. Junior Research Group Molecular Mechanisms of Head and Neck Tumors (A102), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Jennifer Koffler, Gustavo Acuña Sanhueza & Jochen Hess

  4. Division of Signal Transduction and Growth Control (A100), German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Gustavo Acuña Sanhueza

  5. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    Christa Flechtenmacher

  6. Hamamatsu Tissue Imaging and Analysis Center (TIGA), BIOQUANT, Heidelberg University, Im Neuenheimer Feld 267, 69120, Heidelberg, Germany

    Bernd Lahrmann & Niels Grabe

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  1. Jennifer Koffler
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  2. Dana Holzinger
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  3. Gustavo Acuña Sanhueza
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  4. Christa Flechtenmacher
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  5. Karim Zaoui
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  6. Bernd Lahrmann
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  7. Niels Grabe
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  8. Peter K. Plinkert
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  9. Jochen Hess
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Corresponding author

Correspondence to Jochen Hess.

Additional information

J. Koffler and D. Holzinger contributed equally to this study.

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Koffler, J., Holzinger, D., Sanhueza, G.A. et al. Submaxillary gland androgen-regulated protein 3A expression is an unfavorable risk factor for the survival of oropharyngeal squamous cell carcinoma patients after surgery. Eur Arch Otorhinolaryngol 270, 1493–1500 (2013). https://doi.org/10.1007/s00405-012-2201-6

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  • DOI: https://doi.org/10.1007/s00405-012-2201-6

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