PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients - PubMed (original) (raw)

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

M Frattini et al. Br J Cancer. 2007.

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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Figures

Figure 1

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.

Figure 2

Figure 2

PTEN protein expression by immunohistochemistry in metastatic colorectal cancers. (A) Patient showing normal PTEN expression. (B) Patient with absent PTEN expression.

Figure 3

Figure 3

Algorithm in predicting response to cetuximab according to the EGFR and K-Ras status, and PTEN protein expression.

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