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. 2016 Feb;5(2):256-64.
doi: 10.1002/cam4.592. Epub 2015 Dec 29.

KRAS mutation in lung metastases from colorectal cancer: prognostic implications

Michele Ghidini  1 , Nicola Personeni  1   2 , Silvia Bozzarelli  1 , Marina Baretti  1 , Gianluca Basso  3 , Paolo Bianchi  3 , Maria Chiara Tronconi  1 , Tiziana Pressiani  1 , Fabio Grizzi  4 , Laura Giordano  1 , Alberto Malesci  2   5 , Marco Alloisio  1 , Luigi Laghi  3   5 , Armando Santoro  1   6 , Lorenza Rimassa  1
Affiliations

KRAS mutation in lung metastases from colorectal cancer: prognostic implications

Michele Ghidini et al. Cancer Med. 2016 Feb.

Abstract

KRAS mutant colorectal cancer (CRC) patients develop lung and brain metastases more frequently than KRAS wild-type (WT) counterpart. We retrospectively investigated the prognostic role of KRAS, BRAF, and PIK3CA (exon 20) mutations and loss of phosphatase and tensin homolog (PTEN) in surgically resected lung metastases. Lung specimens from 75 metastatic CRC (mCRC) patients treated with one or more metastasectomies with curative intent were analyzed. Sixty-four percent of patients had KRAS WT lung metastases. PTEN loss-of-function was found in 75%. BRAF and PIK3CA exon 20 mutations were not found. Seven patients subsequently developed brain metastases and 43% of them had KRAS mutation. In univariate analysis, median overall survival (OS) for KRAS WT patients was longer, compared to KRAS mutant patients (median 60.9 vs. 36.6 months, P = 0.035). In addition, both progression-free survival (PFS) and lung disease-free survival (LDFS) between lung surgery and relapse were not associated with KRAS and PTEN status. In multivariate analysis, the risk of death was significantly increased by KRAS mutational status (OS Hazard ratio (HR) 2.17, 95% IC 1.19-3.96, P = 0.012) and lack of adjuvant chemotherapy (OS HR 0.10, 95% IC 0.01-0.74, P = 0.024). The proportion of KRAS mutations in lung metastases was similar to the expected proportion in primary tumors. Patients harboring KRAS mutation had a poorer survival rate compared to WT group both in univariate and multivariate analysis. Moreover, administration of adjuvant chemotherapy after lung metastasectomy (LM) significantly improved both PFS and OS. KRAS mutation is a negative prognostic factor in mCRC patients undergoing LM. Further larger and prospective studies are necessary to confirm these findings.

Keywords: BRAF; KRAS; brain metastases; cancer; colorectal; lung metastases.

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Figures

Figure 1
Figure 1
Phosphatase and Tensin Homolog immunohistochemistry (objective magnification 10 × ) (A) positive expression (B) negative expression.
See this image and copyright information in PMC

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