title: An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma.
abstract: Vulvar squamous cell carcinoma (VSCC) is a rare disease that has a high mortality rate (∼40%). However, little is known about its molecular signature. Therefore, an integrated genomics approach, based on comparative genome hybridization (aCGH) and genome-wide expression (GWE) array, was performed to identify driver genes in VSCC. To achieve that, DNA and RNA were extracted from frozen VSCC clinical specimens and examined by aCGH and GWE array, respectively. On the basis of the integration of data using the CONEXIC algorithm, PLXDC2 and GNB3 were validated by RT-qPCR. The expression of these genes was then analyzed by IHC in a large set of formalin-fixed paraffin-embedded specimens. These analyses identified 47 putative drivers, 46 of which were characterized by copy number gains that were concomitant with overexpression and one with a copy number loss and downregulation. Two of these genes, PLXDC2 and GNB3, were selected for further validation: PLXDC2 was downregulated and GNB3 was overexpressed compared with non-neoplastic tissue. By IHC, both proteins were ubiquitously expressed throughout vulvar tissue. High expression of GNB3 and low PLXDC2 immunostaining in the same sample was significantly associated with less lymph node metastasis and greater disease-free survival. On the basis of a robust methodology never used before for VSCC evaluation, two novel prognostic markers in vulvar cancer are identified: one with favorable prognosis (GNB3) and the other with unfavorable prognosis (PLXDC2).
  
  
  
  This genomics study reveals markers that associate with prognosis and may provide guidance for better treatment in vulvar cancer. Mol Cancer Res; 14(8); 720-9. ©2016 AACR.
authors.affiliation: Molecular Morphology Laboratory, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Andre M
authors.initials: AM
authors.lastname: Lavorato-Rocha
authors.affiliation: Molecular Morphology Laboratory, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Akagi
authors.affiliation: Molecular Morphology Laboratory, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Melo Maia
authors.affiliation: Molecular Morphology Laboratory, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Iara S
authors.initials: IS
authors.lastname: Rodrigues
authors.affiliation: Molecular Morphology Laboratory, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Mayara Caroline Silva
authors.initials: MC
authors.lastname: Botelho
authors.affiliation: NeoGene Laboratory, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Marchi
authors.affiliation: Catholic University of Brasília, Brasilia, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fernandes
authors.affiliation: Department of Gynecology Oncology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Glauco
authors.initials: G
authors.lastname: Baiocchi
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: NeoGene Laboratory, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Silvia Regina
authors.initials: SR
authors.lastname: Rogatto
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Sato-Kuwabara
authors.affiliation: Molecular Morphology Laboratory, AC Camargo Cancer Center, São Paulo, Brazil. rafael.malagoli@gmail.com.
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Rocha
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016896:Treatment Outcome; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor