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Coexpression of biological key modulators in primary colorectal carcinomas and related metastatic sites: implications for treatment with cetuximab


Bulletin du Cancer. Volume 97, Number 2, 10009-15, février 2010, Electronic journal of oncology

Free Article  

Author(s) : A Barbier, J Domont, N Magné, J-L Goldmard, C Genestie, C Hannoun, J-C Vaillant, A Bellanger, D Khayat, F Capron, J-P Spano

Summary : BackgroundRecent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases.MethodsExpressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested.ResultsAmong 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38% were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51% were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. A significant correlation was observed between primary tumors and metastases for pAKT (p \= 0.037) and pEGFR (p \= 0.0002) status. In patients treated with cetuximab-based therapy (n \= 18), p21 appeared as a significant predictive factor of response (p \= 0.036).ConclusionBiomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.

Keywords : colorectal cancer, EGFR, metastases, molecular markers, primary tumor, pAKT

 

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