Oral squamous cell carcinoma is a challenging oncology problem. A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined. Using quantitative immunohistochemistry, we examined the expression of vimentin, E-cadherin, and b-catenin in 83 oral squamous cell carcinoma patients, and the relationships between the expression of these markers and specific clinicopathological features were analysed. The high expression of vimentin was observed in 23 of 43 (53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death (Po0.001 and o0.001, respectively). The decreased expression of E-cadherin was observed in 36 of 43 (84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death (Po0.001 and o0.001, respectively). Although no correlation between b-catenin expression in whole-tumour sections and clinicopathological features was observed, decreased b-catenin expression at the tumour invasive front was closely associated with recurrence and death (P ¼ 0.002 and 0.002, respectively). The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses. Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients. The combination of the upregulation of vimentin and aberrant expression of E-cadherin/b-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma. Modern Pathology (2010) 23, 213-224; doi:10.1038/modpathol.2009 published online 13 November 2009 Keywords: vimentin; oral squamous cell carcinoma; immunohistochemistry Oral cancer is the sixth most frequently occurring cancer worldwide, accounting for 3-5% of all malignancies in both sexes.1,2 Over 90% of all oral carcinomas are classified as oral squamous cell carcinoma, which remains a challenging oncology problem.3 Although early-stage oral squamous cell carcinoma can be treated or cured, the prognosis for advanced oral squamous cell carcinoma (stage III and IV) is poor. The treatment of oral squamous cell carcinoma is usually based on surgery or radiation, with or without concomitant chemotherapy. Despite these advanced therapeutic strategies, the 5-year survival rate of oral squamous cell carcinoma (B50%) has not increased over the past four decades.3-5 Local or regional relapse and cervical lymph node metastasis are the most prevalent

The Hippo pathway has emerged as a fundamental regulator in tissue growth, organ size and stem cell functions, and tumorigenesis when deregulated. However, its roles and associated molecular mechanisms underlying oral squamous cell carcinoma (OSCC) initiation and progression remain largely unknown. Here, we identified TAZ, the downstream effector of Hippo signaling, as a novel bona fide oncogene by promoting cell proliferation, migration/invasion and chemoresistance in OSCC. TAZ promoted epithelial-to-mesenchymal transition (EMT) and also was involved in TGF-β1-induced EMT in oral cancer cells. Furthermore, enriched TAZ sustained self-renewal, maintenance, tumor-seeding potential of oral cancer stem cells (CSCs). Remarkably, enforced TAZ overexpression conferred CSCs-like properties on differentiated non-CSCs and fueled phenotypic transition from non-CSCs to CSCs-like cells. Mechanistically, TAZ-TEADs binding and subsequent transcriptional activation of EMT mediators and pluripotency factors are presumably responsible for TAZ-mediated EMT and non-CSCs-to-CSCs conversion. Importantly, aberrant TAZ overexpression was found to be associated with tumor size, pathological grade and cervical lymph node metastasis, as well as unfavorable prognosis. Pharmacological repression of TAZ by simvastatin resulted in potent anti-cancer effects against OSCC. Taken together, our findings have revealed critical links between TAZ, EMT and CSCs in OSCC initiation and progression, and also established TAZ as a novel cancer biomarker and viable druggable target for OSCC therapeutics.

BackgroundBoth tumor-associated macrophages (TAMs) and the epithelial to mesenchymal transition (EMT) of cancer cells play key roles in promoting tumor progression. However, whether TAMs could induce EMT in the progression of oral squamous cell carcinoma (OSCC) remains undefined.ResultsHere we detected the expression of macrophages markers CD68 and CD163, epithelial marker E-cadherin and mesenchymal marker vimentin in 127 OSCC patients by using semi-quantitative immunohistochemistry. CD68 and CD163 expression was not confined to the infiltrating TAMs, but also detected in cancer cells. The high number of CD68-positive macrophages was correlated with poor overall survival. Meanwhile, the expression of CD163 both in macrophages and in cancer cells was associated with poor overall survival and had a significant prognostic impact in OSCC. Importantly, the expression of CD163 in cancer cells had a significant relationship with E-cadherin and vimentin. Furthermore, the incubation of TAMs conditioned medium resulted in a fibroblast-like appearance of cancer cells (HN4, HN6 and SCC9) together with the decreased/increased expression of E-cadherin/ vimentin, which were correlated with the enhanced ability of migration and invasion.ConclusionsOur results indicate that TAMs could promote the EMT of cancer cells, thereby leading to the progression of oral cancer.

Periodontal biotype is used to describe the morphological characteristics of periodontal tissues and is closely related to periodontal health and prognosis of many dental treatments. This study was undertaken to explore the periodontal biotype distribution in a young Chinese population and to evaluate the accuracy of different methods for gingival thickness (GT) measurement. A total of 372 teeth from 31 periodontally healthy subjects were included. GT was measured simultaneously by probe transparency, transgingival probing and cone-beam computed tomography (CBCT). Some other anatomic parameters, including crown width/crown length ratio, attached gingival width, labial bone thickness and papilla volume were recorded for periodontal biotype classification. As found by probe transparency, the gingivae of 222 teeth (59.68%) were thick, while those of 150 teeth (40.32%) were thin. The mean GT of included subjects was 1.03 ± 0.31 mm as measured by transgingival probing and 1.03 ± 0.24 mm as measured by CBCT. Four groups were identified by cluster analysis. Thick-flap biotype, average-scalloped biotype, average-flap biotype and thin-scalloped biotype comprised 137 teeth (36.83%), 96 teeth (25.81%), 39 teeth (10.48%) and 100 teeth (26.88%), respectively. These results demonstrate that the most common periodontal biotype in this young Chinese population was the thick-flap type with low aesthetic risk.

EZH2, a core member of the Polycomb Repressor Complex 2 (PRC2), mediates transcriptional silencing by catalyzing the trimethylation of histone 3 lysine 27 (H3K27), which plays key roles in cancer initiation and progression. Here, we investigated the expression pattern and biological roles of EZH2 in tongue tumorigenesis by loss-of-function assays using small interference RNA and EZH2 inhibitor DZNep. Also we determined the therapeutic efficiency of DZNep against tongue cancer in vivo. We found that aberrantly overexpressed EZH2 was associated with pathological grade, cervical nodes metastasis and Ki-67 expression in tongue cancers. Elevated EZH2 correlated with shorter overall survival and showed significant and independent prognostic importance in patients with tongue cancer. Both genetic and pharmacological depletion of EZH2 inhibited cell proliferation, migration, invasion and colony formation and decreased CD44+ subpopulation probably in part through modulating p16, p21 and E-caherin. Moreover, DZNep enhanced the anticancer effects of 5-Fluorouracil. Furthermore, intratumoral EZH2 inhibition induced by DZNep intraperitoneal administration significantly attenuated tumor growth in a tongue cancer xenograft model. Taken together, our results indicate that EZH2 serves as a key driver with multiple oncogenic functions during tongue tumorigenesis and a new biomarker for tongue cancer diagnosis and prognostic prediction. These findings open up possibilities for therapeutic intervention against EZH2 in tongue cancer.