title: Role of β4 integrin in HER-3-negative, K-RAS wild-type metastatic colorectal tumors receiving cetuximab.
abstract: OBJECTIVE
  Altered α6β4 integrin expression has been demonstrated in HER-3-negative tumors and may be responsible for anti-HER treatment resistance. The current study aimed to evaluate the interaction between polymorphisms of α6 and β4 integrins and clinical outcome in HER-3-negative, K-RAS wild-type colorectal cancer patients receiving cetuximab.
  
  
  METHODS
  K-RAS analysis was performed via direct sequencing, HER-3 was evaluated by immunohistochemistry and genotyping of α6 and β4 integrins was performed by real-time PCR.
  
  
  RESULTS
  An univariate analysis, the β4 rs8669, rs871443 and rs9367 polymorphisms correlated with progression-free and overall survival. On multivariate analysis, only the β4 rs8669 maintained an independent role in influencing progression-free survival.
  
  
  CONCLUSIONS
  We believe that β4 rs8669 genotyping may help to identify a subgroup of HER-3-negative, K-RAS wild-type colorectal cancer patients who are more likely to benefit from anti-EGFR treatment. Our findings could also be relevant in planning future trials testing treatment strategies against the integrin-activated molecular pathways.
authors.affiliation: Clinica di Oncologia Medica, AO Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.forename: Cristian
authors.initials: C
authors.lastname: Loretelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mandolesi
authors.forename: Michela
authors.initials: M
authors.lastname: del Prete
authors.forename: Simona
authors.initials: S
authors.lastname: Biagetti
authors.forename: Simona
authors.initials: S
authors.lastname: Alfonsi
authors.forename: Luca
authors.initials: L
authors.lastname: Faloppi
authors.forename: Maristella
authors.initials: M
authors.lastname: Bianconi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bittoni
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005838:Genotype; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics* / Q000378:metabolism; D039663:Integrin beta4 / Q000235:genetics* / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D020893:Receptor, ErbB-3 / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D039503:Integrin alpha6; D039663:Integrin beta4; C512478:EGFR protein, human; D066246:ErbB Receptors; D020893:Receptor, ErbB-3; D015689:Oncogene Protein p21(ras); D000068818:Cetuximab