Analysis of HER-3, insulin growth factor-1, nuclear factor-kB and epidermal growth factor receptor gene copy number in the prediction of clinical outcome for K-RAS wild-type colorectal cancer patients receiving irinotecan-cetuximab.
Ann Oncol
; 23(7): 1706-12, 2012 Jul.
Article
in En
| MEDLINE
| ID: mdl-22112971
ABSTRACT
BACKGROUND:
A large proportion of colorectal cancer patients does not benefit from the use of anti-epidermal growth factor receptor (EGFR) treatment although in the absence of a mutation of the K-RAS gene. Preliminary observations suggested that HER-3, insulin-like growth factor-1 (IGF-1), nuclear factor-kB (NF-kB) and EGFR gene copy number (GCN) might identify patients not likely to benefit from anti-EGFR therapy. We tested the interaction between HER-3, IGF-1, NF-kB, EGFR GCN and K-RAS mutational analysis to verify the relative ability of these variables to identify a subgroup of patients more likely to benefit from EGFR-targeted treatment among those harbouring a K-RAS wild-type status. PATIENTS ANDMETHODS:
We retrospectively collected tumours from 168 patients with metastatic colorectal cancer treated with irinotecan-cetuximab. K-RAS was assessed with direct sequencing, EGFR amplification was assessed by chromogenic in situ hybridisation (CISH) and HER-3, IGF-1 and NF-kB were assessed by immunohistochemistry.RESULTS:
In patients with K-RAS wild-type tumours, the following molecular factors resulted independently associated with response rate HER-3 [odds ratio (OR)=4.6, 95% confidence interval (CI) 1.8-13.6, P=0.02], IGF-1 (OR=4.2, 95% CI 2-10.2, P=0.003) and EGFR GCN (OR=4.1, 95% CI 1.9-26.2, P=0.04). These factors also independently correlated with overall survival as follows HER-3 [hazard ratio (HR)=0.4, 95% CI 0.28-0.85, P=0.008], IGF-1 (HR=0.47, 95% CI 0.24-0.76, P<0.0001) and EGFR GCN (HR=0.59, 95% CI 0.22-0.89, P=0.04).DISCUSSION:
We believe that our data may help further composing the molecular mosaic of EGFR-resistant tumours. The role of HER-3, IGF-1 and CISH EGFR GCN should be prospectively validated in clinical trials investigating anti-EGFR treatment strategies in colorectal cancer patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin-Like Growth Factor I
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Colorectal Neoplasms
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Antineoplastic Combined Chemotherapy Protocols
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NF-kappa B
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Proto-Oncogene Proteins
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Ras Proteins
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Receptor, ErbB-3
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ErbB Receptors
/
Liver Neoplasms
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Ann Oncol
Journal subject:
NEOPLASIAS
Year:
2012
Type:
Article
Affiliation country:
Italy