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Comparison of KRAS and PIK3CA gene status between primary tumors and paired metastases in colorectal cancer

Authors He Q, Xu Q, Wu W, Chen L, Sun W, Ying J

Received 5 October 2015

Accepted for publication 9 December 2015

Published 20 April 2016 Volume 2016:9 Pages 2329—2335


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Dekuang Zhao

Peer reviewer comments 4

Editor who approved publication: Professor Jianmin Xu

Qiong He,1 Qi Xu,1 Wei Wu,1 Lei Chen,1 Weijing Sun,2 Jieer Ying1

1Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 2Department of Gastrointestinal Medical Oncology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

Purpose: In metastatic or recurrent colorectal cancer (MRCRC), the concordance of Kirsten rat sarcoma viral oncogene homolog (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation status between the primary tumors and metastases is still controversial. The purpose of this study was to evaluate the association between KRAS and PIK3CA mutational status and various clinicopathologic features, and compare their genotype in primary tumors with that of the paired metastatic tumors.
Method: We compared the mutation status of KRAS and PIK3CA between the primary tumors and the paired metastases of 59 MRCRC patients with available tissues (resection or biopsy). The presence of KRAS and PIK3CA mutations were determined by direct sequencing analysis.
Results: Seventeen patients (28.8%) had the KRAS mutation and 46 patients (80.0%) had the PIK3CA mutation when considering both the primary and metastatic sites. KRAS mutation was observed in ten primary tumors and eleven related metastases (16.9% vs 18.6%), while PIK3CA mutation was found in 26 primary tumors and 32 related metastases (44.1% vs 54.2%). KRAS status was concordant between primary and metastatic sites in 45 patients (76.3%, kappa =0.157), while the concordance of PIK3CA status was only found in 25 patients (42.4%, kappa =−0.141). The PIK3CA status discordance rate was significantly higher in 40 patients undergoing metachronous resection of primary tumor or metastasis, compared with that in 19 patients with synchronous resection of primary tumor or metastasis (67.5% [27/40] vs 36.8% [7/19]; P=0.026).
Conclusion: Our results demonstrate that low concordance of KRAS and high discordance of PIK3CA mutational status exist between the primary tumors and paired metastasis, and these findings remind us to have second thoughts about the need to evaluate metastatic tumors separately rather than only based on the primary tumor data when targeted therapy is considered.

Keywords: KRAS, PIK3CA, colorectal cancer, primary tumor, metastatic site

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