TY - JOUR
T1 - Fc gamma receptor IIIa polymorphisms in advanced colorectal cancer patients correlated with response to anti-EGFR antibodies and clinical outcome
AU - Calemma, Rosa
AU - Ottaiano, Alessandro
AU - Trotta, Anna M.
AU - Nasti, Guglielmo
AU - Romano, Carmela
AU - Napolitano, Maria
AU - Galati, Domenico
AU - Borrelli, Pasquale
AU - Zanotta, Serena
AU - Cassata, Antonino
AU - Castello, Giuseppe
AU - Iaffaioli, Vincenzo R.
AU - Scala, Stefania
PY - 2012/11/21
Y1 - 2012/11/21
N2 - 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.
AB - 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.
KW - Antibody-dependent cell-mediated cytotoxicity
KW - Cetuximab
KW - Colorectal cancer
KW - Fc gamma receptor
KW - Panitumumab
KW - Prognosis
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U2 - 10.1186/1479-5876-10-232
DO - 10.1186/1479-5876-10-232
M3 - Article
C2 - 23171437
AN - SCOPUS:84869221346
VL - 10
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
SN - 1479-5876
IS - 1
M1 - 232
ER -