alpha-Smooth muscle actin-positive myofibroblasts, in association with epithelial-mesenchymal transition and lymphogenesis, is a critical prognostic parameter in patients with oral tongue squamous cell carcinoma

作者：Ding Lei; Zhang Ziwen; Shang Duo; Cheng Jie; Yuan Hua; Wu Yunong; Song Xiaoling; Jiang Hongbing^*

来源：Journal of Oral Pathology & Medicine, 2014, 43(5): 335-343.

DOI：10.1111/jop.12143

• lymphogenesis
• oral tongue squamous cell carcinoma
• myofibroblasts
• prognosis
• epithelial-mesenchymal transition

Background
alpha-Smooth muscle actin (alpha-SMA)-positive myofibroblasts play a pivotal role in progression and metastasis of solid carcinomas. Epithelial-mesenchymal transition (EMT) of cancer cells and lymphogenesis of tumor microenvironment are the important events in tumor metastasis. This study aimed to investigate the relationship between the expression of myofibroblasts marker, alpha-SMA, and clinicopathological features, EMT, lymphogenesis, and prognostic status in oral tongue squamous cell carcinoma (OTSCC).
Methods
Immunohistochemisty was used to detect alpha-SMA expression in 50 OTSCCs. EMT and lymphogenesis were also identified by immunostaining with N-cadherin, vimentin, and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1).
Results
There was a significant correlation respectively between the alpha-SMA (P=0.002), vimentin (P<0.001), N-cadherin (P=0.025) expression and cervical lymph node metastasis of OTSCC. Carcinomas with alpha-SMA (P=0.001), vimentin (P=0.003), and N-cadherin (P=0.012) expression were more advanced in terms of tumor-node-metastases status. Univariate analysis showed that pathologic node status (P<0.001), alpha-SMA (P=0.001), and vimentin expression (P=0.044) was significantly associated with overall survival time, but multivariate analysis just showed the alpha-SMA expression (P=0.008) and pathologic node status (P=0.003) was independently predictive of prognosis. Furthermore, statistical analysis showed significant correlation between alpha-SMA expression and vimentin (P=0.037), N-cadherin (P=0.019), or LYVE-1 positive vessel count (P=0.041).
Conclusion
Our results indicate that alpha-SMA-positive myofibroblasts have important impacts on cancer progression, metastasis, and survival prognosis of patients with OTSCC. The functions of alpha-SMA-positive myofibroblasts in OTSCC may be associated with promoting EMT of tumor cells and lymphogenesis of metastasis microenvironment.

• 出版日期2014-5
• 单位南京医科大学