Abstract

In the present study, we explored the expression and correlation of survivin with HIF-1α, TGF-β1 and TFE3 in adenoid cystic carcinoma (AdCC). The expression of survivin, HIF-1α, TGF-β1 and TFE3 was assessed by immunohistochemical staining of a tissue microarray containing tissue samples of normal salivary gland (NSG), pleomorphic adenoma (PA) and AdCC. Correlation analysis of these proteins revealed that increased survivin expression was associated with the overexpression of HIF-1α (P<0.001, r = 0.5599), TGF-β1 (P<0.001, r = 0.6616) and TFE3 (P<0.001, r = 0.7747). The expression of survivin, HIF-1α, TGF-β1 and TFE3 was not correlated with the pathological type of human AdCC (P>0.05). Selective inhibition of survivin by YM155 and siRNA significantly reduced human SACC-83 cell proliferation, with the corresponding decrease in expression of HIF-1α, TGF-β1 and TFE3. The data indicate that the overexpression of survivin in AdCC is related to HIF-1α, TGF-β1 and TFE3. We hypothesize from these findings that the inhibition of survivin may be a novel strategy for neoadjuvant chemotherapeutic and radiosensitive treatment of AdCC.

Highlights

  • Adenoid cystic carcinoma (AdCC) is one of the most common primary malignancies of the major and minor salivary glands [1]

  • Normal salivary gland samples (18 parotid glands and 7 submandibular glands), 12 pleomorphic adenoma (PA) samples and 72 AdCC samples were selected for the immunohistochemical staining of survivin, HIF-1a, Transforming growth factor-beta 1 (TGF-b1) and Transcription factor E3 (TFE3) antibody-stained array (S1 Datasheet)

  • We reported the expression of survivin and certain hypoxia related HIF-1a and TGF-b1 that were highly expressed in AdCC

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Summary

Introduction

Adenoid cystic carcinoma (AdCC) is one of the most common primary malignancies of the major and minor salivary glands [1]. Unlike head and neck squamous cell carcinoma, AdCC is characterized by neural infiltration and PLOS ONE | DOI:10.1371/journal.pone.0114051. The elucidation of the molecular events of AdCC is urgently required. AdCC is characterized by basaloid tumor consisting of epithelial and myoepithelial cells in variable morphologic configurations, including tubular, cribriform and solid patterns [4]. Some AdCC especially solid type may have difficult of differential diagnosis from mucoepidermoid carcinoma (MEC). Pleomorphic adenoma (PA) is and most common benign tumor of salivary gland with epithelial and modified myoepithlial elements intermingles with tissue of mucoid, myxoid or chondroid appearance [4]

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