European Archives of Oto-Rhino-Laryngology

, Volume 270, Issue 4, pp 1493–1500 | Cite as

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

  • Jennifer Koffler
  • Dana Holzinger
  • Gustavo Acuña Sanhueza
  • Christa Flechtenmacher
  • Karim Zaoui
  • Bernd Lahrmann
  • Niels Grabe
  • Peter K. Plinkert
  • Jochen HessEmail author
Head and Neck


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.


Opiorphin Oropharyngeal cancer SMR3A Surgery Tissue microarray 



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.

Supplementary material

405_2012_2201_MOESM1_ESM.docx (14 kb)
Supplementary Material 1 (DOC 15 kb)
405_2012_2201_MOESM2_ESM.tif (275 kb)
Supplementary Material 2 (TIF 275 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jennifer Koffler
    • 1
    • 3
  • Dana Holzinger
    • 2
  • Gustavo Acuña Sanhueza
    • 1
    • 3
    • 4
  • Christa Flechtenmacher
    • 5
  • Karim Zaoui
    • 1
  • Bernd Lahrmann
    • 6
  • Niels Grabe
    • 6
  • Peter K. Plinkert
    • 1
  • Jochen Hess
    • 1
    • 3
    Email author
  1. 1.Experimental Head and Neck Oncology, Department of Otolaryngology, Head and Neck SurgeryUniversity Hospital HeidelbergHeidelbergGermany
  2. 2.Division of Genome Modifications and Carcinogenesis (F020), Infection and Cancer ProgramGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Junior Research Group Molecular Mechanisms of Head and Neck Tumors (A102)German Cancer Research Center (DKFZ), DKFZ-ZMBH AllianceHeidelbergGermany
  4. 4.Division of Signal Transduction and Growth Control (A100)German Cancer Research Center (DKFZ), DKFZ-ZMBH AllianceHeidelbergGermany
  5. 5.Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany
  6. 6.Hamamatsu Tissue Imaging and Analysis Center (TIGA), BIOQUANTHeidelberg UniversityHeidelbergGermany

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