title: Multivariate analyses of Ki-67, cytokeratin 13 and cytokeratin 17 in diagnosis and prognosis of oral precancerous lesions.
abstract: BACKGROUND
  Ki-67, cytokeratin 13, and/or cytokeratin 17 detection by immunohistochemistry has been reported to be useful for the diagnosis of oral precancerous lesions. However, the use of these markers remains controversial because of the lack of appropriately designed statistical studies. We assessed the hypothesis that Ki-67, cytokeratin 13, or cytokeratin 17 immunohistochemistry could facilitate the diagnosis of oral precancerous lesions and/or predict prognosis.
  
  
  METHODS
  Epithelial dysplasia was classified as low grade (none or mild dysplasia) or high grade (moderate dysplasia, severe dysplasia, or carcinoma in situ). This study included 58 low-grade and 36 high-grade dysplasia cases. We used logistic regression to assess the diagnostic values of Ki-67, cytokeratin 13, and cytokeratin 17 for high-grade dysplasia. Correlations between these markers and the prognosis of oral atypical epithelium were assessed using the Cox proportional hazards model.
  
  
  RESULTS
  Ki-67 overexpression and cytokeratin 13 loss were independent diagnostic markers for high-grade dysplasia (odds ratios, 1.92 and 2.53; 95% confidence intervals, 1.03-3.58, and 1.19-5.38, respectively). The area under the curve of Ki-67 was 0.73 and that of cytokeratin 13 was 0.72. However, the combination of Ki-67 and cytokeratin 13 yielded the area under the curve of 0.78. Ki-67 overexpression was significantly associated with recurrence and/or malignant transformation of oral atypical epithelium (hazard ratio, 7.25; 95% confidence interval, 1.07-48.92).
  
  
  CONCLUSIONS
  Ki-67 overexpression and cytokeratin 13 loss may be useful for distinguishing oral precancerous lesions from reactive atypical epithelium. Moreover, Ki-67 overexpression may be a risk factor for recurrence and/or malignant transformation of oral atypical epithelium.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Nara, Japan.|Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yagyuu
authors.affiliation: Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Chiho
authors.initials: C
authors.lastname: Obayashi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ueyama
authors.affiliation: Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Takano
authors.affiliation: Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Yuu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kawaguchi
authors.affiliation: Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Kasai
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis; D002278:Carcinoma in Situ / Q000737:chemistry / Q000175:diagnosis; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053535:Keratin-13 / Q000032:analysis*; D053537:Keratin-17 / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology; D009062:Mouth Neoplasms / Q000737:chemistry / Q000175:diagnosis*; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000175:diagnosis; D011230:Precancerous Conditions / Q000737:chemistry / Q000175:diagnosis*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C507426:KRT13 protein, human; D053535:Keratin-13; D053537:Keratin-17; D019394:Ki-67 Antigen
keywords: Ki-67; cytokeratin 13; multivariate analysis; oral precancerous lesions; reactive atypical epithelium