Fc gamma receptor IIIa polymorphisms in advanced colorectal cancer patients correlated with response to anti-EGFR antibodies and clinical outcome

Journal of Translational Medicine

Stefania Scala³  Vincenzo Rosario Iaffaioli²  Giuseppe Castello¹  Antonino Cassata²  Serena Zanotta³  Pasquale Borrelli³  Domenico Galati³  Maria Napolitano³  Carmela Romano²  Guglielmo Nasti²  Anna Maria Trotta³  Alessandro Ottaiano²  Rosa Calemma³ 

[1] CROM - Centro Ricerche Oncologiche di Mercogliano, "Fiorentino Lo Vuolo", Via Ammiraglio Bianco, Mercogliano, (AV), Italy;Abdominal Oncology, National Cancer Institute “G. Pascale”, via M. Semmola, Naples, 80131, Italy;Oncological Immunology, National Cancer Institute “G. Pascale”, via M. Semmola, Naples 80131, Italy

关键词: Antibody-dependent cell-mediated cytotoxicity;    Panitumumab;    Cetuximab;    Prognosis;    Colorectal cancer;    Fc gamma receptor;   

Others  :  828748
DOI  :  10.1186/1479-5876-10-232

 received in 2012-06-05, accepted in 2012-10-24,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Calemma et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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