title: α-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.
abstract: BACKGROUND
  α-Smooth muscle actin (α-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, α-SMA, and clinicopathological features, EMT, lymphogenesis, and prognostic status in oral tongue squamous cell carcinoma (OTSCC).
  
  
  METHODS
  Immunohistochemisty was used to detect α-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 α-SMA (P = 0.002), vimentin (P < 0.001), N-cadherin (P = 0.025) expression and cervical lymph node metastasis of OTSCC. Carcinomas with α-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), α-SMA (P = 0.001), and vimentin expression (P = 0.044) was significantly associated with overall survival time, but multivariate analysis just showed the α-SMA expression (P = 0.008) and pathologic node status (P = 0.003) was independently predictive of prognosis. Furthermore, statistical analysis showed significant correlation between α-SMA expression and vimentin (P = 0.037), N-cadherin (P = 0.019), or LYVE-1 positive vessel count (P = 0.041).
  
  
  CONCLUSIONS
  Our results indicate that α-SMA-positive myofibroblasts have important impacts on cancer progression, metastasis, and survival prognosis of patients with OTSCC. The functions of α-SMA-positive myofibroblasts in OTSCC may be associated with promoting EMT of tumor cells and lymphogenesis of metastasis microenvironment.
authors: Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Nanjing, China; Institute of Stomatology, Nanjing Medical University, Nanjing, China.
authors: Lei
authors: L
authors: Ding
authors: Ziwen
authors: Z
authors: Zhang
authors: Duo
authors: D
authors: Shang
authors: Jie
authors: J
authors: Cheng
authors: Hua
authors: H
authors: Yuan
authors: Yunong
authors: Y
authors: Wu
authors: Xiaoling
authors: X
authors: Song
authors: Hongbing
authors: H
authors: Jiang
mesh_terms: D000199:Actins / Q000032:analysis*; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000556:secondary; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis / Q000473:pathology; D042601:Lymphatic Vessels / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000737:chemistry / Q000473:pathology* / Q000502:physiology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000737:chemistry / Q000473:pathology*; D059016:Tumor Microenvironment; D033921:Vesicular Transport Proteins / Q000032:analysis; D014746:Vimentin / Q000032:analysis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C119248:LYVE1 protein, human; D033921:Vesicular Transport Proteins; D014746:Vimentin
keywords: epithelial-mesenchymal transition; lymphogenesis; myofibroblasts; oral tongue squamous cell carcinoma; prognosis