Cited by 540Colorectal Cancer Treatments and StudiesLung Cancer Treatments and MutationsHER2/EGFR in Cancer Research

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PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients

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Frattini, M, Saletti, P, Romagnani, E, Martin, V, Molinari, F, Ghisletta, M, Camponovo, A, Etienne, L L, Cavalli, F, Mazzucchelli, L·2007·British Journal of Cancer

DOI 10.1038/sj.bjc.6604009PMC PMC2360431

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Abstract

To evaluate whether the epidermal growth factor receptor (EGFR), K-Ras and PTEN, all members of the EGFR signalling pathway, may affect the clinical response in cetuximab-treated metastatic colorectal cancer (mCRC) patients. Twenty-seven cetuximab-treated mCRC patients were evaluated for drug response and investigated for EGFR protein expression and gene status, K-Ras mutational status and PTEN protein expression. Ten patients achieved a partial response (PR) to cetuximab-based therapy. All 27 patients showed EGFR protein overexpression. Epidermal growth factor receptor gene amplification was observed in eight out of 27 (30%) and chromosome 7 marked polysomy in 16 (59%) patients. Partial response was observed in six out of eight patients with EGFR gene amplification, four out of 16 with marked polysomy and none out of three with eusomy (P<0.05). The K-Ras wild-type sequence was observed in 17 patients, and nine of them experienced a PR. Conversely, K-Ras was mutated in 10 cases, of which one patient experienced a PR (P<0.05). The PTEN protein was normally expressed in 16 patients, and 10 of them achieved a PR. In contrast, no benefit was documented in 11 patients with loss of PTEN activity (P<0.001). Patients with EGFR gene amplification or chromosome 7 marked polysomy respond to cetuximab. In addition to K-Ras mutations, we demonstrate for the first time that the loss of PTEN protein expression is associated with nonresponsiveness to cetuximab.

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Figure 1 Epidermal growth factor receptor gene status evaluated by FISH in metastatic colorectal cancers. (A) Patient showing eusomy of chromosome 7. (B) Patient with marked polysomy on chromosome 7. (C) Patient with EGFR gene amplification in at least 10% of tumoral cells.CC BY · PubMed Central

Figure 2 PTEN protein expression by immunohistochemistry in metastatic colorectal cancers. (A) Patient showing normal PTEN expression. (B) Patient with absent PTEN expression.CC BY · PubMed Central

Figure 3 Algorithm in predicting response to cetuximab according to the EGFR and K-Ras status, and PTEN protein expression.CC BY · PubMed Central

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“More importantly, the recently published report by Frattini et al [10] also examined PTEN by IHC and discovered a correlation between loss of PTEN protein expression and lack of response to cetuximab.”
BackgroundInfluential

Authors: Frattini, M., Saletti, P., Romagnani, E., Martin, V, Molinari, F., Ghisletta, M., Camponovo, A., Etienne, L. L., Cavalli, F., & Mazzucchelli, L.
Affiliations: Istituto Cantonale di Patologia (CH)
Ospedale San Giovanni Bellinzona (CH)
Corresponding author: Frattini, M
ORCID: Frattini, M
Cavalli, F
Venue: British Journal of Cancer
Publisher: Springer Science and Business Media LLC
Published: 2007-10
Volume: 97
Issue: 8
Pages: 1139-1145
ISSN: 0007-0920 (ISSN-L)
1532-1827
DOI: 10.1038/sj.bjc.6604009
PMC: PMC2360431
OpenAlex: W2100589633
Cited by: 540
References: 31
Citations by year: 2026: 3 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 14 · 2020: 16 · 2019: 14 · 2018: 9 · 2017: 15 · 2016: 20 · 2015: 30 · 2014: 38 · 2013: 38 · 2012: 63
FWCI: 33.57
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
www.springer.com/tdm (unspecified)
Locations: British Journal of Cancer (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Oncosuisse
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Keywords: PTEN loss, cetuximab, metastatic colorectal cancer, EGFR overexpression, EGFR amplification, KRAS mutation, chromosome 7 polysomy, drug response prediction, predictive biomarkers
MeSH terms: Cetuximab, Adult, Aged, Algorithms, Antibodies, Monoclonal, Antineoplastic Agents, Chromosomes, Human, Pair 7, Female, Gene Amplification, Humans, Immunohistochemistry, Male, Middle Aged, Proto-Oncogene Proteins, Biomarkers, Tumor, Colorectal Neoplasms, Gene Expression, Proto-Oncogene Proteins p21(ras), In Situ Hybridization, Fluorescence, ras Proteins, Drug Resistance, Neoplasm, PTEN Phosphohydrolase, Antibodies, Monoclonal, Humanized, ErbB Receptors

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PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients

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