PMID- 21042730
OWN - NLM
STAT- MEDLINE
DCOM- 20110224
LR  - 20191210
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 37
IP  - 6
DP  - 2010 Dec
TI  - FcgammaR polymorphisms and clinical outcome in colorectal cancer patients receiving 
      passive or active antibody treatment.
PG  - 1599-606
AB  - Fcgamma receptors (FcgammaRs) on effector cells are of importance for mediating 
      antibody-dependent cellular cytotoxicity (ADCC). FcgammaRIIIa158valine 
      (V)/phenylalanine (F) and FcgammaRIIa131histidine (H)/arginine(R) polymorphisms have 
      been shown to relate to prognosis in antibody-treated patients. The aim of the 
      present study was to analyze the polymorphisms of both FcgammaRIIIa and FcgammaRIIa in 
      colorectal carcinoma (CRC) patients receiving either passively administered 
      monoclonal antibodies (MAbs) or antibodies induced by carcinoembryonic antigen 
      (CEA) vaccination. One hundred and thirty CRC patients were included. 
      Thirty-eight patients received adjuvant treatment with an anti-EpCAM monoclonal 
      antibody (edrecolomab) (n=17) or rCEA vaccination therapeutic cancer vaccine 
      (TCV) (n=21) inducing anti-CEA IgG antibodies. Ninety-two patients had metastatic 
      disease and received anti-EpCAM MAb based therapies. FcgammaR genotypes were analysed 
      using genomic DNA and PCR. ADCC was tested in a standard 18 h Cr51 release assay. 
      In all adjuvant-treated patients, FcgammaRIIIa158V carriers (V/V and V/F) had a 
      significantly better overall survival compared to F/F homozygous patients 
      (p<0.05), FcgammaRIIa R carriers vs. H/H (p=0.05) as well as V and R carriers 
      combined compared to the others (p<0.05). Similar findings were obtained when 
      antibody and TCV-treated patients were analysed separately. No impact on the 
      prognosis of FcgammaR polymorphisms was noted in advanced disease. FcgammaRIIIa V 
      carriers had a significantly higher ADCC activity compared to F/F patients 
      (p=0.001). Our model study might support the notion that FcgammaRIIIa V carriers as 
      well as FcgammaRIIa R carriers receiving adjuvant, passively or actively 
      (TCV)-induced antibody treatment might have a better prognosis than the others. 
      Prospective extended clinical trials are warranted to study the 
      predictive/prognostic impact of FcgammaR polymorphisms in antibody-treated patients 
      and might be a valuable biomarker to optimize antibody-based treatment 
      strategies.
FAU - Wang, Biyun
AU  - Wang B
AD  - Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Department of 
      Oncology-Pathology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
FAU - Kokhaei, Parviz
AU  - Kokhaei P
FAU - Mellstedt, Hakan
AU  - Mellstedt H
FAU - Liljefors, Maria
AU  - Liljefors M
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Antibodies)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies/*therapeutic use
MH  - Carcinoembryonic Antigen/immunology
MH  - Carcinoma/*diagnosis/genetics/immunology/pathology/*therapy
MH  - Colorectal Neoplasms/*diagnosis/genetics/immunology/pathology/*therapy
MH  - Female
MH  - Humans
MH  - Immunization, Passive/methods
MH  - Immunotherapy, Active/methods
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide/physiology
MH  - Prognosis
MH  - Receptors, IgG/*genetics/metabolism
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2010/11/03 06:00
MHDA- 2011/02/25 06:00
CRDT- 2010/11/03 06:00
PHST- 2010/11/03 06:00 [entrez]
PHST- 2010/11/03 06:00 [pubmed]
PHST- 2011/02/25 06:00 [medline]
AID - 10.3892/ijo_00000814 [doi]
PST - ppublish
SO  - Int J Oncol. 2010 Dec;37(6):1599-606. doi: 10.3892/ijo_00000814.