Molecular Profiling of Brain Metastases from Colorectal Cancer
Giovanna De Maglio, Eufemia S Lutrino, Sara Cernic, Francesco Tuniz, Mariaelena Casagrande, Giovanni Falconieri, Giuseppe Aprile, Miran Skrap, Gianpiero Fasola, Stefano Pizzolitto. University Hospital S. Maria della Misericordia, Udine, Italy
Background: Brain metastasis (BM) from colorectal cancer (CRC) are reported with increased frequency, likely due to improved survival for patients with advanced disease. Furthermore surgical resection of oligometastatic disease may produce survival benefits in appropriated candidates. There is limited data suggesting that KRAS/BRAF mutations prevalence may differ depending on metastatic site and KRAS mutation status is more frequent in brain than in liver lesions. However, to the best of our knowledge specific studies addressing the molecular profile of BM from CRC are not available.
Design: We identified a cohort of 46 consecutive patients with CRC who underwent resection of BM. A total of 39 routinely processed tissue specimens were retrieved, histologically reviewed, macrodissected, and tested by pyrosequencing with Anti-EGFR MoAb response® KRAS status, BRAF, PIK3CA, NRAS (Diatech pharmacogenetics, Italy) kits accordingly to manufacturer's instructions. KRAS has been tested for codons 12, 13, 61 and 146, BRAF for exon 15, PIK3CA for exons 9 and 20 and NRAS for codons 12, 13 and 61.
Results: Median age at time of BM biopsy was 65 yrs (35-82). Median survival following craniotomy was 163 days (4-1976). In BM from CRC, any KRAS mutation was detected in 22 patients (56,4%). Specifically, 15 patients (38,5%) harbored mutations on codon 12 (G12V, G12D, G12A, G12C, G12S), 5 (12,8%) on codon 13 (G13D and G13C), and 2 (5,1%) on codon 146 (A146V). Among patients with wild-type status for KRAS, 3 (7,7%) harbored V600E BRAF mutation. PIK3CA was mutated in 5 (12,8%) patients (4 on exon 19: E542K, E545K and Q546K, 1 on exon 20, H1047R); PIK3CA/KRAS mutations were concomitant in 3 cases. No NRAS mutations were detected. All wild-type patients were 12 (30,8%). Median survival was similar between patients with all wild-type tumors and patients harboring any mutation in the EGFR-pathway.
Conclusions: KRAS, BRAF and PIK3CA were identified as the main mutation targets in brain metastases. This is in keeping with known oncogene profiling studies in primary colorectal cancers. Somatic changes in the EGFR-KRAS pathway members were mutually exclusive except for PIK3CA and KRAS with no prevalence of any particular mutation. KRAS mutation rate (56.4%) in BM was higher than expected in primary CRC, as previously reported in literature.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 272, Tuesday Afternoon