EGFR fluorescence in situ hybridization pattern of chromosome 7 disomy predicts resistance to cetuximab in KRAS wild-type metastatic colorectal cancer patients.
OBJECTIVE
Metastatic colorectal cancer patients with low epidermal growth factor receptor (EGFR) gene copy number are unlikely to respond to anti-EGFR monoclonal antibody (mAb) treatment. The objective of this study was to investigate EGFR fluorescence in situ hybridization (FISH) patterns of chromosome 7 disomy with efficacy of cetuximab therapy in metastatic colorectal cancer patients.


METHODS
We detected the EGFR FISH patterns and KRAS status in 74 tumors from cetuximab-treated metastatic colorectal cancer patients and analyzed with response rate (RR) and progression-free survival (PFS).


RESULTS
One of the 16 (6.25%) patients with chromosome 7 homogeneous disomy (defined as FISH negative) had objective response to cetuximab. A total of 53(76.8%) patients with chromosome 7 pattern of variable ratios of disomy versus polysomy (defined as FISH positive) had a significantly higher RR (37.7% versus 6.25%; P = 0.01), a trend towards longer PFS (4.5 versus 2.9 months; P = 0.07). Among 54 KRAS wild-type patients, EGFR FISH-positive patients had significantly higher RR (51.3% versus 9%; P = 0.01) and longer PFS (5.0 versus 2.3 months; P = 0.02) than EGFR FISH-negative patients. However, among 20 KRAS mutant-type patients, there was no difference in RR (0% versus 0%) and PFS (2.5 versus 3.8 months; P = 0.51) between EGFR FISH-positive and -negative patients.


CONCLUSIONS
Our results show firstly that patients with EGFR FISH pattern of chromosome 7 disomy have a very low chance to benefit from cetuximab-based therapy. EGFR FISH pattern of chromosome 7 disomy may be as a negative predicative factor for cetuximab response in KRAS wild-type metastatic colorectal cancer patients.
Li
Yu-Hong
YH
State Key Laboratory of Oncology in Southern China, Guangzhou, People's Republic of China.
Wang
Fang
F
Shen
Lin
L
Deng
Yan-Ming
YM
Shao
Qiong
Q
Feng
Fen
F
An
Xin
X
Wang
Feng-Hua
FH
Wang
Zhi-Qiang
ZQ
Xu
Rui-Hua
RH
Shao
Jian-Yong
JY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D002897:Chromosomes, Human, Pair 7; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000276:immunology; D005260:Female; D018628:Gene Dosage; D018773:Genes, erbB-1; D011905:Genes, ras; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D024182:Uniparental Disomy
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D000068818:Cetuximab