European Archives of Oto-Rhino-Laryngology

, Volume 269, Issue 4, pp 1073–1083 | Cite as

Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review

  • Juan P. Rodrigo
  • Juana María García-Pedrero
  • Carlos Suárez
  • Robert P. Takes
  • Lester D. R. Thompson
  • Pieter J. Slootweg
  • Julia A. Woolgar
  • William H. Westra
  • Ruud H. Brakenhoff
  • Alessandra Rinaldo
  • Kenneth O. Devaney
  • Michelle D. Williams
  • Douglas R. Gnepp
  • Alfio Ferlito
Review article


Some laryngeal epithelial precursor lesions progress to invasive carcinoma and others do not. Routine light microscopic classification has limited value in predicting the evolution of these lesions. This article reviews the experience to date with the use of molecular markers for the prognostic evaluation of laryngeal epithelial precursor lesions. We conducted a thorough review of the published literature to identify those studies using biomarkers to predict malignant progression of laryngeal epithelial precursor lesions. Of the 336 studies identified in this systematic search, 15 met the inclusion criteria and form the basis of this review. Limited studies suggest that certain biomarkers are potentially reliable predictors of malignant progression including various regulators of cell adhesion and invasion (e.g. FAK, cortactin, osteopontin, and CD44v6) and proliferation-associated markers such as TGF-βRII and Kv3.4. The predictive value of these markers, however, has yet to be confirmed in large-scale prospective studies. Although the cell cycle-related proteins are the most frequently studied markers, none have been consistently reliable across multiple studies. The absence of standardization in methodologies, test interpretation, and other parameters may contribute to study inconsistencies. Various biomarkers have proved to have potential prognostic value and could be clinically relevant. The utility and prognostic power of these biomarkers should be confirmed in large, well-designed, standardized prospective studies.


Larynx Epithelial precursor lesions Dysplasia Carcinoma in situ Biomarkers 


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Juan P. Rodrigo
    • 1
    • 2
  • Juana María García-Pedrero
    • 1
    • 2
  • Carlos Suárez
    • 1
    • 2
  • Robert P. Takes
    • 3
  • Lester D. R. Thompson
    • 4
  • Pieter J. Slootweg
    • 5
  • Julia A. Woolgar
    • 6
  • William H. Westra
    • 7
  • Ruud H. Brakenhoff
    • 8
  • Alessandra Rinaldo
    • 9
  • Kenneth O. Devaney
    • 10
  • Michelle D. Williams
    • 11
  • Douglas R. Gnepp
    • 12
  • Alfio Ferlito
    • 9
  1. 1.Department of OtolaryngologyHospital Universitario Central de AsturiasOviedoSpain
  2. 2.Instituto Universitario de Oncología del Principado de AsturiasOviedoSpain
  3. 3.Department of Otolaryngology-Head and Neck SurgeryRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  4. 4.Department of PathologyWoodland Hills Medical CenterWoodland HillsUSA
  5. 5.Department of PathologyRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  6. 6.Oral Pathology, School of Dental Sciences and Dental HospitalUniversity of LiverpoolLiverpoolUK
  7. 7.Departments of Pathology and Otolaryngology-Head and Neck SurgeryThe Johns Hopkins Medical InstitutionsBaltimoreUSA
  8. 8.Department of Otolaryngology-Head and Neck SurgeryVU University Medical CenterAmsterdamThe Netherlands
  9. 9.ENT ClinicUniversity of UdineUdineItaly
  10. 10.Department of PathologyAllegiance HealthJacksonUSA
  11. 11.Department of PathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  12. 12.Department of PathologyWarren Alpert School of Medicine at Brown University, Rhode Island HospitalProvidenceUSA

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