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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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.
KeywordsOpiorphin 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.
- 6.Kostareli E, Holzinger D, Hess J (2012) New concepts for translational head and neck oncology: lessons from HPV-related oropharyngeal squamous cell carcinomas. Front Head Neck Cancer 2:1–10Google Scholar
- 13.Holzinger D, Schmitt M, Dyckhoff G, Benner A, Pawlita M, Bosch FX (2012) Viral RNA patterns and high viral load reliably define oropharynx carcinomas with active HPV16 involvement. Cancer Res doi: 10.1158/0008-5472.CAN-11-3934
- 22.Papandreou CN, Usmani B, Geng Y, Bogenrieder T, Freeman R, Wilk S, Finstad CL, Reuter VE, Powell CT, Scheinberg D, Magill C, Scher HI, Albino AP, Nanus DM (1998) Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression. Nat Med 4:50–57PubMedCrossRefGoogle Scholar