Epidermal Growth Factor Receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis
Open accessAbstract
BACKGROUND: K-RAS wild type colorectal tumors show an improved response rate to anti-EGFR monoclonal antibodies. Nevertheless 70% to 40% of these patients still does not seem to benefit from this therapeutic approach. FISH EGFR GCN has been previously demonstrated to correlate with clinical outcome of colorectal cancer treated with anti-EGFR monoclonal antibodies. CISH also seemed able to provide accurate EGFR GCN information with the advantage of a simpler and reproducible technique involving immunohistochemistry and light microscopy. Based on these findings we investigated the correlation between both FISH and CISH EGFR GCN and clinical outcome in K-RAS wild-type colorectal cancer treated with irinotecan-cetuximab. METHODS: Patients with advanced K-RAS wild-type, colorectal cancer receiving irinotecan-cetuximab after failure of irinotecan-based chemotherapy were eligible. A cut-off value for EGFR GCN of 2.6 and 2.12 for FISH and CISH respectively was derived from ROC curve analysis. RESULTS: Forty-four patients were available for analysis. We observed a partial remission in 9 (60%) and 2 (9%) cases with a FISH EGFR GCN >or= 2.6 and < 2.6 respectively (p = 0.002) and in 10 (36%) and 1 (6%) cases with a CISH EGFR GCN >or= 2.12 and < 2.12 respectively (p = 0.03). Median TTP was 7.7 and 6.4 months in patients showing increased FISH and CISH EGFR GCN whereas it was 2.9 and 3.1 months in those with low FISH and CISH EGFR GCN (p = 0.04 and 0.02 respectively). CONCLUSION: FISH and CISH EGFR GCN may both represent effective tools for a further patients selection in K-RAS wild-type colorectal cancer treated with cetuximab.
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Increased EGFR gene copy number could predict response among KRAS wild-type patients.
“Increased EGFR gene copy number could predict response among KRAS wild-type patients [53, 91, 111-113]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [111]
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- Authors
- Scartozzi, M., Bearzi, I., Mandolesi, A., Pierantoni, C., Loupakis, F., Zaniboni, A., Negri, F., Quadri, A., Zorzi, F., Galizia, E., Berardi, R., Biscotti, T., Labianca, R., Masi, G., Falcone, A., & Cascinu, S.
- Affiliations
- Marche Polytechnic University (IT)
- Ospedale di Livorno (IT)
- Fondazione Poliambulanza Istituto Ospedaliero (IT)
- Corresponding author
- Scartozzi, Mario
- ORCID
- Venue
- BMC Cancer
- Published
- 2009-08-27
- Volume
- 9
- Issue
- 1
- Pages
- 303-303
- ISSN
- 1471-2407 (ISSN-L)
- PMC
- PMC3087339
- OpenAlex
- W2001454653
- Cited by
- 72
- References
- 24
- Citations by year
- 2022: 1 · 2021: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 10 · 2014: 7 · 2013: 9 · 2012: 10
- FWCI
- 5.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- EGFR gene copy number, cetuximab, irinotecan, anti-EGFR monoclonal antibody, fluorescence in situ hybridization, chromogenic in situ hybridization, predictive biomarkers, treatment response, time to progression, patient selection
- MeSH terms
- Cetuximab, Irinotecan, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Female, Humans, Male, Middle Aged, Mutation, Retrospective Studies, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Treatment Failure, In Situ Hybridization, In Situ Hybridization, Fluorescence, Gene Dosage, ras Proteins, Antibodies, Monoclonal, Humanized, ErbB Receptors
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