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RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer
Author(s) -
Yaeger Rona,
Cowell Elizabeth,
Chou Joanne F.,
Gewirtz Alexandra N.,
Borsu Laetitia,
Vakiani Efsevia,
Solit David B.,
Rosen Neal,
Capanu Marinela,
Ladanyi Marc,
Kemeny Nancy
Publication year - 2015
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.29196
Subject(s) - medicine , kras , neuroblastoma ras viral oncogene homolog , colorectal cancer , oncology , brain metastasis , metastasis , incidence (geometry) , exon , multivariate analysis , mutation , bone metastasis , cumulative incidence , cancer , biology , cohort , gene , genetics , physics , optics
BACKGROUND RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. METHODS We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site‐specific metastasis. RESULTS Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS ). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P < .01). RAS mutant mCRC exhibited a significantly higher cumulative incidence of lung, bone, and brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site‐specific pattern of metastatic spread. CONCLUSIONS The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site‐specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. Cancer 2015;121:1195–1203. © 2014 American Cancer Society .