Developmental transcription factor EN1--a novel biomarker in human salivary gland adenoid cystic carcinoma

Cancer. 2012 Mar 1;118(5):1288-92. doi: 10.1002/cncr.26412. Epub 2011 Jul 28.


Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by histogenetic, morphologic, and clinical heterogeneity. Extensive efforts to characterize the molecular events associated with these tumors have included the identification of biomarkers for prognostication and post-therapy assessment. In a previous study of genome-wide methylation screening, the authors of the current report identified a limited number of differentially methylated gene regions in ACC, and significant hypermethylation was observed at the transcriptional start sites of genes that encode for the transcription factor engrailed homeobox 1 (EN1). Clinicopathologic correlation analyses indicated that EN1 methylation status is correlated with histologic tumor grade, tumor location, and final patient outcome. To ascertain definitively whether aberrant EN1 expression accompanies human salivary ACC, the authors used an immunohistochemical technique to directly evaluate EN1 protein expression in ACC of the salivary gland. The data revealed increased EN1 protein expression in solid type ACC, which was correlated with a significantly lower survival rate. The current results validated EN1 as a potential biomarker in a large cohort of patients with salivary ACC. Immunohistochemical analysis of EN1 in biopsy specimens obtained for diagnostic purposes and/or surgically resected material may reveal that EN1 is a biologic predictor of poor prognosis in patients with salivary ACC.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Biomarkers, Tumor* / physiology
  • Carcinoma, Adenoid Cystic / diagnosis*
  • Carcinoma, Adenoid Cystic / genetics
  • Carcinoma, Adenoid Cystic / metabolism
  • Carcinoma, Adenoid Cystic / mortality
  • Gene Expression Regulation, Neoplastic
  • Genes, Developmental / physiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Homeodomain Proteins / physiology*
  • Humans
  • Middle Aged
  • Prognosis
  • Salivary Gland Neoplasms / diagnosis*
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / mortality
  • Survival Analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology
  • Young Adult


  • Biomarkers, Tumor
  • EN1 protein, human
  • Homeodomain Proteins
  • Transcription Factors