Research Papers:

Expression of the extracellular sulfatase SULF2 is associated with squamous cell carcinoma of the head and neck

Sarah A. Flowers, Xin Zhou, Jing Wu, Yiwen Wang, Kepher Makambi, Bhaskar V. Kallakury, Mark S. Singer, Steven D. Rosen, Bruce Davidson and Radoslav Goldman _

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Oncotarget. 2016; 7:43177-43187. https://doi.org/10.18632/oncotarget.9506

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Sarah A. Flowers1,*, Xin Zhou1,*, Jing Wu1, Yiwen Wang1, Kepher Makambi1, Bhaskar V. Kallakury2, Mark S. Singer3, Steven D. Rosen3, Bruce Davidson4, Radoslav Goldman1,5

1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA

2Department of Pathology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA

3Department of Anatomy, University of California, San Francisco, CA 94143, USA

4Department of Otolaryngology-Head and Neck Surgery, Medstar Georgetown University Hospital, Washington, DC 20057, USA

5Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC 20057, USA

*Co-first author

Correspondence to:

Radoslav Goldman, email: [email protected]

Keywords: heparan sulfate proteoglycans, biomarker, sulfation, cancer progression, tumorigenesis

Received: January 14, 2016     Accepted: April 16, 2016     Published: May 20, 2016


Sulfatase 2 (SULF2), an extracellular sulfatase that alters sulfation on heparan sulfate proteoglycans, is involved in the tumorigenesis and progression of several carcinomas. SULF2 expression has not been evaluated in squamous cell carcinoma of the head and neck (HNSCC). Here we report results of IHC of SULF2 expression in HNSCC tissue. SULF2 was detected in 57% of tumors (n = 40) with a significant increase in intensity and number of stained cells compared to adjacent cancer-free tissue (p-value < 0.01), increasing with cancer stage when comparing stages 1 and 2 to stages 3 and 4 (p-value 0.01). SULF2 was not detected in epithelial cells of cancer-free controls, and expression was independent of patient demographics, tumor location and etiological factors, smoking and HPV infection by p16 IHC analysis. Sandwich ELISA was performed on serum of HNSCC patients (n = 28) and controls (n = 35), and although SULF2 was detectable, no change was observed in HNSCC. Saliva, collected by mouthwash, from HNSCC patients (n = 8) and controls (n = 8) was also tested by ELISA in a preliminary investigation and an increase in SULF2 was observed in HNSCC (p-value 0.041). Overall, this study shows that SULF2 is increased in HNSCC independent of tissue location (oral cavity, oropharynx, larynx and hypopharynx), patient demographics and etiology. Although no change in SULF2 was detected in HNSCC serum, its detection in saliva makes it worthy of further investigation as a potential HNSCC biomarker.

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