title: Fc gamma receptor IIIa polymorphisms in advanced colorectal cancer patients correlated with response to anti-EGFR antibodies and clinical outcome.
abstract: BACKGROUND
  Anti-EGFR monoclonal antibodies have shown efficacy in the treatment of metastatic colorectal cancer (mCRC). One of the mechanism is the antibody-dependent cell-mediated cytotoxicity (ADCC) in which Fc region of the antibody binds to the Fc gamma receptors (FcγR) expressed by immune cells. The present study investigated the association between single nucleotide polymorphisms of FcγRIIa and FcγRIIIa and clinical outcome in mCRC treated with anti-EGFR antibodies.
  
  
  METHODS
  Seventy-four consecutive patients with mCRC were analyzed. The genotypes for FcγRIIa-131 histidine (H)/arginine (R), FcγRIIIa-158 valine (V)/phenylanaline (F) polymorphisms were evaluated by directly sequencing. Multiplex allele-specific polymerase chain reaction was performed for FcγRIIIa-158 valine (V)/phenylanaline (F). Correlations between FcγR polymorphisms, baseline patient and tumor features were studied by contingency tables and the chi-square test. The Kaplan-Meier product limit method was applied to the progression-free survival (PFS) curves. Univariate analysis was performed with the log-rank test. Cox proportional-hazards regression was used to analyze the effect of multiple risk factors on PFS.
  
  
  RESULTS
  FcγRIIIa polymorphisms were significantly associated with response to anti-EGFR-based therapy in 49 patients with kras wt tumors (p=0.035). There was not association with response for FcγRIIa polymorphisms. Furthermore, obtained results suggested that prognosis is particularly unfavorable for patients carrying the FcγRIIIa-158F/F genotype (median PFS V/V, V/F, F/F: 18.2 vs 17.3 vs 9.4 months). No prognostic ability was identified for FcγRIIa polymorphisms.
  
  
  CONCLUSIONS
  In mCRC patients the presence of FcγRIIIa-F can predict resistance to anti-EGFR therapy and unfavorable prognosis.
authors.affiliation: Oncological Immunology, National Cancer Institute "G, Pascale", Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Calemma
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ottaiano
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Trotta
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Nasti
authors.forename: Carmela
authors.initials: C
authors.lastname: Romano
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Domenico
authors.initials: D
authors.lastname: Galati
authors.forename: Pasquale
authors.initials: P
authors.lastname: Borrelli
authors.forename: Serena
authors.initials: S
authors.lastname: Zanotta
authors.forename: Antonino
authors.initials: A
authors.lastname: Cassata
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
authors.forename: Vincenzo Rosario
authors.initials: VR
authors.lastname: Iaffaioli
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D017452:Receptors, IgG / Q000235:genetics*; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; C496124:FCGR3A protein, human; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins