title: Overexpression of SIP1 and downregulation of E-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy.
abstract: BACKGROUND
  Patients with clinical stage I/II (T1-2N0M0) oral tongue squamous cell carcinoma (TSCC) usually undergo partial glossectomy alone. However, 14-48% of them develop delayed neck metastasis (DNM), which may lead to an unfavorable course. Recently epithelial-to-mesenchymal transition (EMT) has been thought to play a crucial role in cancer metastasis. The present study aimed to examine the associations of EMT-involved molecular factors and clinicopathological factors with DNM in stage I/II TSCC.
  
  
  METHODS
  mRNA expression levels of E-cadherin and its transcriptional repressors (snail, SIP1, and twist) in 7 head and neck squamous cell carcinoma (HNSCC) cell lines were evaluated by quantitative real-time PCR. Clinicopathological parameters and immunohistochemical expressions of E-cadherin and its repressors were examined in surgical specimens of 37 stage I/II TSCC patients who underwent partial glossectomy alone.
  
  
  RESULTS
  In HNSCC cells, E-cadherin expression was inversely correlated with SIP1 expression (P = 0.023). Univariate analysis of immunohistochemistry showed that overexpression of SIP1 and loss of E-cadherin were significantly correlated with DNM, although no inverse correlation was found between E-cadherin and its repressors. Multiple logistic regression analysis including clinicopathological and molecular factors revealed that overexpression of SIP1 (P = 0.005), loss of E-cadherin (P = 0.046), and vascular invasion (P = 0.024) were independently correlated with DNM.
  
  
  CONCLUSIONS
  These results suggest that development of DNM in stage I/II TSCC is closely related to induction of EMT in primary tumor cells. Especially, SIP1 and E-cadherin are considered to be the possible markers for selecting patients at high risk of DNM.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Imanishi
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tomita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimoda
authors.forename: Kaori
authors.initials: K
authors.lastname: Kameyama
authors.forename: Katsushi
authors.initials: K
authors.lastname: Shibata
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sakai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ozawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Shigetomi
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Fujii
authors.forename: Masato
authors.initials: M
authors.lastname: Fujii
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005927:Glossectomy; D006801:Humans; D007124:Immunoenzyme Techniques; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins