title: Predictive markers for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral tongue.
abstract: OBJECTIVE
  Patients with oral tongue carcinoma treated by intraoral excision only should be followed up carefully for cervical lymph node metastasis and salvaged immediately if found, because some patients have a more aggressive clinical course. The purpose of this study was to find useful markers for predicting late cervical metastasis in patients with stage I and II invasive squamous cell carcinoma of the oral tongue.
  
  
  METHODS
  We investigated clinicopathologic factors and immunohistochemical biomarkers predicting late cervical metastasis in surgical specimens from 56 patients with T(1-2)N(0)M(0) invasive squamous cell carcinoma of the oral tongue who did not undergo elective neck dissection. Histopathologic factors including tumor thickness, mode of invasion, Broders grade, total score of three different malignancy grading systems, eight other clinicopathologic parameters, and immunohistochemical expression of p53, cyclin D1, Ki-67, epidermal growth factor receptor, microvessel density, cyclooxygenase-2, MUC1, laminin-5 gamma2, E-cadherin, and beta-catenin were examined. All of the clinicopathologic factors and immunohistochemical expression of biomarkers were compared in terms of survival.
  
  
  RESULTS
  In the univariate analysis, tumor thickness (P = 0.009), Broders grade (P = 0.017), nest shape (P = 0.005), mode of invasion (P < 0.001), Anneroth score (P = 0.029), Bryne score (P < 0.001), and E-cadherin expression (P = 0.003) were correlated with late cervical metastasis. Multivariate analysis on late cervical metastasis revealed that tumor thickness >4 mm, mode of invasion grade 3 or 4, and E-cadherin expression were independent factors. Late cervical metastasis was the only prognostic factor for overall survival (P = 0.002).
  
  
  CONCLUSIONS
  Our results indicate that patients with stage I and II invasive squamous cell carcinoma of the oral tongue with tumor thickness >4 mm, mode of invasion grade 3 or 4, and low expression of E-cadherin should be considered a high-risk group for late cervical metastasis when a wait-and-see policy for the neck is adopted.
authors.affiliation: Pathology Division, National Cancer Center Research Institute East, Chiba, Japan.
authors.forename: Sang-Chul
authors.initials: SC
authors.lastname: Lim
authors.forename: Shichuan
authors.initials: S
authors.lastname: Zhang
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Endoh
authors.forename: Keiji
authors.initials: K
authors.lastname: Kodama
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ebihara
authors.forename: Jae-Shik
authors.initials: JS
authors.lastname: Cho
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality / Q000556:secondary*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009333:Neck; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor