Abstract
Background: Colorectal cancers (CRC) with brain metastases (BM) are scarcely described. The main objective of this study was to determine the molecular profile of CRC with BM. Methods: We included 82 CRC patients with BM. KRAS, NRAS, BRAF and mismatch repair (MMR) status were investigated on primary tumors (n = 82) and BM (n = 38). ALK, ROS1, cMET, HER-2, PD-1, PD-L1, CD3 and CD8 status were evaluated by immunohistochemistry, and when recommended, by fluorescence in situ hybridization. Results: In primary tumors, KRAS, NRAS and BRAF mutations were observed in 56%, 6%, and 6% of cases, respectively. No ROS1, ALK and cMET rearrangement was detected. Only one tumor presented HER-2 amplification. Molecular profiles were mostly concordant between BM and paired primary tumors, except for 9% of discordances for RAS mutation. CD3, CD8, PD-1 and PD-L1 expressions presented some discordance between primary tumors and BM. In multivariate analysis, multiple BM, lung metastases and PD-L1+ tumor were predictive of poor overall survival. Conclusions: CRCs with BM are associated with high frequency of RAS mutations and significant discordance for RAS mutational status between BM and paired primary tumors. Multiple BM, lung metastases and PD-L1+ have been identified as prognostic factors and can guide therapeutic decisions for CRC patients with BM.
Highlights
Brain metastases (BM) from colorectal cancer (CRC) are rare with an incidence ranging from 0.6 to3.2% and are associated with a poor prognosis with an overall survival (OS) of about 5.0 months [1,2].Patients with brain metastases (BM) from Colorectal cancers (CRC) present a specific clinical profile with predominant rectosigmoid primaryCancers 2018, 10, 504; doi:10.3390/cancers10120504 www.mdpi.com/journal/cancersCancers 2018, 10, 504 tumor location and lung metastases [3,4,5,6]
Our study provided relevant and specific features of CRC patients with BM, such as frequent lung metastasis, frequent rectal tumor site and high rate of RAS mutation
These results suggest a need for BM screening in this metastatic CRC (mCRC) patients subgroup, but will require further prospective investigations to determine if early identification of BM improves survival and/or quality of life
Summary
Cancers 2018, 10, 504 tumor location and lung metastases [3,4,5,6]. Some small series have suggested a high rate of KRAS mutation in CRC with BM, but no study has evaluated complete RAS (KRAS and NRAS), BRAF and mismatch repair (MMR) status [1]. In metastatic CRC (mCRC), molecular profiles of liver and lung metastases have already been tested and revealed a high concordance between the metastases and paired primary tumor (PPT). KRAS, NRAS, BRAF and mismatch repair (MMR) status were investigated on primary tumors (n = 82) and BM (n = 38). Results: In primary tumors, KRAS, NRAS and BRAF mutations were observed in 56%, 6%, and 6% of cases, respectively. Molecular profiles were mostly concordant between BM and paired primary tumors, except for 9% of discordances for RAS mutation
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