title: EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions.
abstract: OBJECTIVE
  Promoter hypermethylation has been recently proposed as a means for head and neck squamous cell carcinoma (HNSCC) detection in salivary rinses. In a prospective study of a high-risk population, we showed that endothelin receptor type B (EDNRB) promoter methylation in salivary rinses is a useful biomarker for oral cancer and premalignancy.
  
  
  METHODS
  Using that cohort, we evaluated EDNRB methylation status and 8 additional genes. Clinical risk assessment by expert clinicians was conducted and compared with biomarker performance in the prediction of premalignant and malignant disease. Methylation status of 9 genes was analyzed in salivary rinses of 191 patients by quantitative methylation-specific PCR.
  
  
  RESULTS
  HOXA9, EDNRB, and deleted in colorectal cancer (DCC) methylation were associated (P = 0.012; P < 0.0001; P = 0.0005) with premalignant or malignant disease. On multivariable modeling, histological diagnosis was only independently associated with EDNRB (P = 0.0003) or DCC (P = 0.004) methylation. A subset of patients received clinical risk classification (CRC) by expert clinicians based on lesion examination. CRC, DCC, and EDNRB were associated with diagnosis of dysplasia/cancer on univariate (P = 0.008; P = 0.026; P = 0.046) and multivariate analysis (P = 0.012; P = 0.037; P = 0.047). CRC identified dysplasia/cancer with 56% of sensitivity and 66% of specificity with a similar area under curve [AUC; 0.61, 95% confidence interval (CI) = 0.60-0.81] when compared to EDNRB and DCC combined AUC (0.60, 95% CI = 0.51-0.69), sensitivity of 46% and specificity of 72%. A combination of EDNRB, DCC, and CRC was optimal AUC (0.67, 95% CI = 0.58-0.76).
  
  
  CONCLUSIONS
  EDNRB and/or DCC methylation in salivary rinses compares well to examination by an expert clinician in CRC of oral lesions. These salivary biomarkers may be particularly useful in oral premalignancy and malignancy screening in clinical care settings in which expert clinicians are not available.
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors: Juliana
authors: J
authors: Schussel
authors: Xian Chong
authors: XC
authors: Zhou
authors: Zhe
authors: Z
authors: Zhang
authors: Kavita
authors: K
authors: Pattani
authors: Francisco
authors: F
authors: Bermudez
authors: Germain
authors: G
authors: Jean-Charles
authors: Thomas
authors: T
authors: McCaffrey
authors: Tapan
authors: T
authors: Padhya
authors: Joan
authors: J
authors: Phelan
authors: Silvia
authors: S
authors: Spivakovsky
authors: Mariana
authors: M
authors: Brait
authors: Ryan
authors: R
authors: Li
authors: Helen Yoo
authors: HY
authors: Bowne
authors: Judith D
authors: JD
authors: Goldberg
authors: Linda
authors: L
authors: Rolnitzky
authors: Miriam
authors: M
authors: Robbins
authors: A Ross
authors: AR
authors: Kerr
authors: David
authors: D
authors: Sirois
authors: Joseph A
authors: JA
authors: Califano
mesh_terms: D014408:Biomarkers, Tumor; D000075389:DCC Receptor; D019175:DNA Methylation; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D017466:Receptors, Endothelin / Q000096:biosynthesis*; D012463:Saliva / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D000075389:DCC Receptor; C501909:DCC protein, human; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D025521:Tumor Suppressor Proteins
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