Does Testing of KRAS in Patients with Metastatic Colorectal Cancer Offer Valuable Information in Deciding Treatment Options?
C Bossard, P Jamet, S Bezieau, S Kury, F Airaud, H Senellart, T Matysiak-Budnik, JF Mosnier. CHU Hotel Dieu, Nantes, France; Faculte de Medecine, Nantes, France; Centre Rene Gauducheau, Nantes, France
Background: Several studies demonstrated that patients with metastatic colorectal cancer (mCRC) without KRAS mutation benefit from therapy with monoclonal antibodies directed against the EGFR. However, only 20 to 50% of patients with KRAS wild-type status respond to this treatment. To explore whether this “resistance” could be in part explained by a molecular heterogeneity, we compared KRAS and BRAF gene status between primary tumor and matched metastases in patients with mCRC.
Design: Mutational status of KRAS (codons 12, 13) and BRAF (codon 600) genes was evaluated retrospectively in primary CRC (n=24) and matched synchronous and/or metachronous metastases (n=33) or in local recurrence (n=1) from 20 patients. The number of metastases available per patient was comprised between 1 and 4. Mutation analysis was performed by means of direct sequencing of PCR products obtained from genomic DNA extracted from histologicaly macrodissected paraffin-embedded tissue sections. Only tissue samples containing at least 50% of tumor cells were studied.
Results: KRAS mutation was found in 10 of 20 (50%) primary CRC, 16 of 31 (51%) metastases, and in one local recurrence. No BRAF V600E mutation was found. In 10 of 17 (58%) available pairs, KRAS status was concordant between primary CRC and metastases. In 7 of 17 (41%) pairs, KRAS status was discordant : in 2 cases, mutation was present in primary CRC but absent in synchronous metastasis; in 1 case, mutation was detected only in local recurrence; in 1 case, mutation was absent in primary CRC and in 1 synchronous metastasis but present in two others, synchronous and metachronous; in 1 case, mutation was found in primary CRC and in synchronous metastasis but absent in metachronous one; in 2 patients with synchronous multifocal CRC, discordant results were found between primary CRC, between metastases, and between CRC and metastases.
Conclusions: This study demonstrates a significant genotypic heterogeneity in CRC between primary tumor and matched metastases. These data raise the question of whether testing of KRAS in patients with mCRC offers really valuable information in deciding treatment options.
Monday, March 22, 2010 9:00 AM
Platform Session: Section E, Monday Morning