Abstract 2979: Wolf-Hirschhorn syndrome candidate 1 plays an important role in the pathogenesis of head and neck cancer.

Abstract

Abstract Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a histone lysine methyltransferase (HMT) which was initially found to be deregulated in a subset of multiple myeloma cells with the t(4;14) (p16;q32) translocation and poor prognosis. Recently, our group as well as others found that WHSC1 was overexpressed in a variety of tumors, including lung and esophageal squamous cell carcinomas, with low or no expression in normal tissues except the testis. Long-term survival of patients with squamous cell carcinoma of the head and neck (SCCHN) remains poor and thus new therapeutic strategies are urgently needed. Epigenetic alterations have mainly been studied as a potential mechanism of progression from dysplasia to squamous cell carcinoma. Given the promising potential of HMTs as novel drug targets and the aforementioned interesting expression patterns, we further investigated the role of WHSC1 in carcinogenesis through immunohistochemical analysis (IHC) using tissue microarrays of 123 locoregionally advanced SCCHN patients, and 6 samples of fibroepithelial hyperplasia lesions obtained from oral biopsies. We classified its expression levels with a scoring scale of 0 (no expression), +1 (mild), +2 (moderate) or +3 (strong). WHSC1 expression in the nucleus and cytoplasm was moderate (score +2, 37%) or strong (score +3, 38%) in 75% of SCCHN samples, while 25% showed mild (score +1, 24%) or no (score 0, 1%) expression. WHSC1 staining of normal epithelial regions revealed an exclusively nuclear expression pattern in the basal and parabasal layers. This is consistent with reports suggesting a physiologic role of the Wnt-pathway, which was recently found to be induced by WHSC1, in the differentiation process of the squamous epithelium. We also performed Western blot analysis of WHSC1 in 8 SCCHN cells lines, 3 control fibroblast cell lines and 1 keratinocyte cell line. We observed moderate to strong overexpression of WHSC1 in 4 of 8 SCCHN cell lines, while no expression was detected in the normal keratinocytes or the fibroblast cell lines. These findings support a potential role of the WHSC1 pathway in the pathogenesis of SCCHN and provides a new therapeutic avenue for drug discovery in this fatal disease. Citation Format: Vassiliki Saloura, Hyun-Soo Cho, Mark Lingen, Terri Li, Can Gong, Seiwert Tanguy, Ezra Cohen, Ryuji Hamamoto, Yusuke Nakamura. Wolf-Hirschhorn syndrome candidate 1 plays an important role in the pathogenesis of head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2979. doi:10.1158/1538-7445.AM2013-2979