Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage

Julia Thierauf; Stephanie E Weissinger; Johannes A Veit; Annette Affolter; Natalia K Laureano; Dirk Beutner; Gregor Heiduschka; Lorenz Kadletz; Moritz Meyer; Alexander Quaas; Peter Plinkert; Thomas K Hoffmann; Jochen Hess

doi:10.1371/journal.pone.0194989

Low SOX2 expression marks a distinct subset of adenoid cystic carcinoma of the head and neck and is associated with an advanced tumor stage

PLoS One. 2018 Mar 29;13(3):e0194989. doi: 10.1371/journal.pone.0194989. eCollection 2018.

Authors

Julia Thierauf^{1

2}, Stephanie E Weissinger³, Johannes A Veit², Annette Affolter^{1

4}, Natalia K Laureano^{1

5

6}, Dirk Beutner^{7

8}, Gregor Heiduschka⁹, Lorenz Kadletz⁹, Moritz Meyer⁷, Alexander Quaas¹⁰, Peter Plinkert¹, Thomas K Hoffmann², Jochen Hess^{1

5}

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University Hospital, Heidelberg, Germany.
² Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Ulm, Ulm, Germany.
³ Institute of Pathology, University Medical Center Ulm, Ulm, Germany.
⁴ Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
⁵ Research Group Molecular Mechanisms of Head and Neck Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶ Department of Oral Pathology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
⁷ Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Cologne, Cologne, Germany.
⁸ Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Göttingen, Göttingen, Germany.
⁹ Department of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Vienna, Austria.
¹⁰ Institute of Pathology, University Hospital Cologne, Cologne, Germany.

Abstract

Introduction: The transcription factor SOX2 has been identified as a lineage survival oncogene in squamous cell carcinoma and copy number gain is a common event in several human malignancies including head and neck cancer. However, the regulation and function of SOX2 during carcinogenesis as well as its prognostic value appears to be highly context dependent. As an example, high SOX2 expression in lung squamous cell carcinoma (SCC) is related to a favorable prognosis, while it is associated with poor outcome in lung adenocarcinoma. More recently, higher SOX2 levels and improved survival was also reported for head and neck SCC (HNSCC), and silencing of SOX2 expression in HNSCC cell lines revealed a mesenchymal-like phenotype with prominent vimentin expression. So far, SOX2 expression and its clinical relevance for other head and neck cancers, such as adenoid cystic carcinoma (HNACC) have not been sufficiently investigated.

Material and methods: SOX2, vimentin and E-cadherin expression was assessed by immunohistochemical staining on serial sections from formalin fixed and paraffin embedded tissue samples of a patient cohort (n = 45) with primary ACC and correlated with patient and tumor characteristics as well as survival.

Results: High SOX2 expression was found in 14 (31%) primary tumor specimens and was significantly correlated with a N0 lymph node status (p = 0.04), while low SOX2 expression was correlated with a solid growth pattern (p = 0.031). Of the 45 patients, 27 tumor samples resembled an EMT-like phenotype, as assessed by high vimentin and low E-cadherin levels. However, in HNACC SOX2 levels were neither correlated with vimentin nor with E-cadherin expression, further supporting a context dependent regulation and function of SOX2 in distinct tumor entities.

Conclusion: The absence of SOX2 was predominantly found in solid HNACC, which are characterized by a more aggressive phenotype in ACC. However, the underlying molecular mechanisms of SOX2 regulation and function in distinct HNACC subgroups remain to be fully elucidated.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cadherins / metabolism
Carcinoma, Adenoid Cystic / metabolism*
Carcinoma, Adenoid Cystic / pathology*
Female
Gene Expression Regulation, Neoplastic*
Head and Neck Neoplasms / metabolism*
Head and Neck Neoplasms / pathology*
Humans
Male
Middle Aged
Neoplasm Staging
SOXB1 Transcription Factors / metabolism*
Vimentin / metabolism

Substances

Cadherins
SOX2 protein, human
SOXB1 Transcription Factors
Vimentin

Grants and funding

This study was funded by the Alexander-Karl-Price of the Stiftung Tumorforschung Kopf-Hals to JT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.