Expression profiling on subclasses of primary parotid gland carcinomas.

INTRODUCTION

The underlying molecular mechanisms of parotid gland carcinomas (PGC) are still unknown. Knowledge about the tumor-driving signaling pathways is necessary either for diagnostics or developing new therapeutic options in this heterogeneous and rare entity.

MATERIAL AND METHODS

94 matching RNA formalin-fixed and paraffin-embedded tissue samples from PGC and the corresponding non-tumor area, RNA quality and quantity were sufficient for gene expression profiling of 770 genes using the NanoString's nCounter technology. Oncogenic and tumor suppressor genes were examined in the three common PGC tumor entities: adenoid cystic carcinoma (ACC), adenocarcinoma NOS (AC-NOS), and mucoepidermoid carcinoma (MEC).

RESULTS

Expression profiling and subsequent hierarchical cluster analysis clearly differentiated between non-tumor gland tissue samples and PGC. In addition expression pattern of all three entities differed. The extensive pathway analysis proved a prominent dysregulation of the Wnt signaling pathway in the three PGC entities. Moreover, transcript upstream analysis demonstrated a pronounced activation of the PI3K pathway in ACC and MEC.

DISCUSSION

Our findings revealed divergent molecular expression profiles in MEC, ACC and AC-NOS that are presently studied for their potential application in PGC diagnostics. Importantly, identification of Wnt and PI3K signaling in PGC revealed novel options of PGC therapy.