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

• Published in: PloS one 2018-03, Vol.13 (3), p.e0194989
• Main Authors: Thierauf, Julia, Weissinger, Stephanie E, Veit, Johannes A, Affolter, Annette, Laureano, Natalia K, Beutner, Dirk, Heiduschka, Gregor, Kadletz, Lorenz, Meyer, Moritz, Quaas, Alexander, Plinkert, Peter, Hoffmann, Thomas K, Hess, Jochen
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenoid; Biology and Life Sciences; Carcinogenesis; Carcinogens; Care and treatment; Cell survival; Copy number; Correlation; Development and progression; Dissection; E-cadherin; Gene amplification; Gene expression; Genetic aspects; Head; Head & neck cancer; Head and neck cancer; Health aspects; Lung cancer; Lung carcinoma; Lymph nodes; Lymphatic system; Medical prognosis; Medical research; Medicine and Health Sciences; Melanoma; Mesenchyme; Metastasis; Molecular modelling; Motility; Neck; Otolaryngology; Paraffin; Pathology; Phenotypes; Skin cancer; Squamous cell carcinoma; Subgroups; Surgery; Survival; Transcription factors; Tumors; Vimentin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0194989

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. 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. 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. 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.