title: Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review.
abstract: 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.
authors.affiliation: Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Rodrigo
authors.forename: Juana María
authors.initials: JM
authors.lastname: García-Pedrero
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.forename: Robert P
authors.initials: RP
authors.lastname: Takes
authors.forename: Lester D R
authors.initials: LD
authors.lastname: Thompson
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Slootweg
authors.forename: Julia A
authors.initials: JA
authors.lastname: Woolgar
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rinaldo
authors.forename: Kenneth O
authors.initials: KO
authors.lastname: Devaney
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Williams
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Gnepp
authors.forename: Alfio
authors.initials: A
authors.lastname: Ferlito
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D006801:Humans; D007820:Laryngeal Mucosa / Q000473:pathology*; D007830:Larynx / Q000473:pathology*; D010610:Pharyngeal Neoplasms / Q000097:blood* / Q000473:pathology; D011230:Precancerous Conditions / Q000097:blood* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
references.citation: Mod Pathol. 2011 Jul;24(7):892-8
references.pmid: 21499237
references.citation: Clin Cancer Res. 1999 Jun;5(6):1243-8
references.pmid: 10389906
references.citation: Cancer Prev Res (Phila). 2011 Aug;4(8):1333-41
references.pmid: 21646305
references.citation: Cancer. 2006 Aug 1;107(3):563-9
references.pmid: 16804930
references.citation: Clin Otolaryngol Allied Sci. 2004 Dec;29(6):698-704
references.pmid: 15533163
references.citation: J Clin Oncol. 2005 Dec 20;23(36):9067-72
references.pmid: 16172462
references.citation: BMC Cancer. 2010 Aug 10;10:416
references.pmid: 20698954
references.citation: N Engl J Med. 2007 Dec 20;357(25):2539-41
references.pmid: 18094374
references.citation: N Engl J Med. 2008 Sep 11;359(11):1143-54
references.pmid: 18784104
references.citation: Cancer Res. 1996 May 1;56(9):2199-205
references.pmid: 8616872
references.citation: Head Neck Pathol. 2009 Mar;3(1):63-8
references.pmid: 20596993
references.citation: J Clin Pathol. 2001 Mar;54(3):201-4
references.pmid: 11253131
references.citation: J Natl Cancer Inst. 1997 Aug 6;89(15):1161-3
references.pmid: 9262255
references.citation: Clin Otolaryngol. 2010 Jun;35(3):170-6
references.pmid: 20636735
references.citation: J Pathol. 2010 Aug;221(4):402-10
references.pmid: 20593490
references.citation: Mol Cancer. 2010 Mar 02;9:48
references.pmid: 20196862
references.citation: Nat Rev Cancer. 2011 Jan;11(1):9-22
references.pmid: 21160525
references.citation: Eur Arch Otorhinolaryngol. 2006 Sep;263(9):843-52
references.pmid: 16823559
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):973-8
references.pmid: 17210912
references.citation: Int J Cancer. 1994 Jan 2;56(1):95-9
references.pmid: 7903288
references.citation: J Membr Biol. 2005 Jun;205(3):115-24
references.pmid: 16362499
references.citation: Head Neck. 2011 Aug;33(8):1170-6
references.pmid: 21755560
references.citation: Cancer Res. 1996 Jun 1;56(11):2488-92
references.pmid: 8653682
references.citation: J Clin Oncol. 2008 Jan 20;26(3):354-60
references.pmid: 18202409
references.citation: Acta Otolaryngol. 2006 Apr;126(4):418-21
references.pmid: 16608796
references.citation: J Pathol. 1992 Sep;168(1):85-6
references.pmid: 1453271
references.citation: Nat Rev Mol Cell Biol. 2003 Jan;4(1):33-45
references.pmid: 12511867
references.citation: Histopathology. 2000 Nov;37(5):460-3
references.pmid: 11119129
references.citation: Cancer Res. 2006 Aug 15;66(16):8017-25
references.pmid: 16912177
references.citation: Br J Cancer. 2007 Dec 3;97(11):1545-51
references.pmid: 17987038
references.citation: J Laryngol Otol. 1998 May;112(5):455-9
references.pmid: 9747474
references.citation: J Cell Biochem. 1996 Jan;60(1):23-32
references.pmid: 8825412
references.citation: Acta Otolaryngol Suppl. 1997;527:30-8
references.pmid: 9197477
references.citation: Cancer Prev Res (Phila). 2009 Jan;2(1):14-21
references.pmid: 19139013
references.citation: Am J Otolaryngol. 1996 Jan-Feb;17(1):36-44
references.pmid: 8801814
references.citation: Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3272-9
references.pmid: 16740747
references.citation: Histopathology. 2009 May;54(6):639-56
references.pmid: 18752537
references.citation: Head Neck Pathol. 2010 Dec;4(4):276-80
references.pmid: 20857246
references.citation: Cancer Radiother. 2001 Apr;5(2):109-29
references.pmid: 11355576
references.citation: J Pathol. 2009 Mar;217(4):516-23
references.pmid: 18991334
references.citation: Cancer Lett. 1999 Aug 23;143(1):23-8
references.pmid: 10465333
references.citation: Nat Rev Cancer. 2005 Jul;5(7):505-15
references.pmid: 16069815
references.citation: Trends Cell Biol. 2006 Feb;16(2):79-87
references.pmid: 16406521