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Meta-Analysis
. 2015 Feb 2:5:8065.
doi: 10.1038/srep08065.

Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases

Chen Mao  1 , Xin-Yin Wu  2 , Zu-Yao Yang  2 , Diane Erin Threapleton  2 , Jin-Qiu Yuan  2 , Yuan-Yuan Yu  2 , Jin-Ling Tang  1
Affiliations
Meta-Analysis

Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases

Chen Mao et al. Sci Rep. .

Abstract

Current data on the concordance of KRAS, BRAF, PIK3CA mutation status or PTEN expression status between primary tumors and metastases in colorectal cancer (CRC) are conflicting. We conducted a systematic review and meta-analysis to examine concordance and discordance of the status of these four biomarkers between primary tumors and corresponding metastases in CRC patients. The biomarker status in primary tumors was used as the reference standard. Concordance data for KRAS, BRAF, PIK3CA and PTEN were provided by 43, 16, 9 and 7 studies, respectively. The pooled concordance rate was 92.0% (95% CI: 89.7%-93.9%) for KRAS, 96.8% (95% CI: 94.8%-98.0%) for BRAF, 93.9% (95% CI: 89.7%-96.5%) for PIK3CA and 71.7% (95% CI: 57.6%-82.5%) for PTEN. The pooled false positive and false negative rates for KRAS were 9.0% (95% CI: 6.5%-12.4%) and 11.3% (95% CI: 8.0%-15.8%), respectively. KRAS, BRAF and PIK3CA mutations are highly concordant between primary tumors and corresponding metastases in CRC, but PTEN loss is not. Nine percent of patients with wild-type KRAS in primary tumors who received anti-EGFR treatment had mutant KRAS in metastases, while 11.3% patients with mutant KRAS primary tumors had wild-type KRAS in the metastases. These 11.3% patients currently do not receive potentially beneficial anti-EGFR treatment.

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Figures

Figure 1
Figure 1. Flow chart of study selection.
Figure 2
Figure 2. Pooled false positive rate and false negative rate for KRAS mutations in patients with colorectal cancer.
Figure 3
Figure 3. Discordance on mutation status of KRAS between primary tumor and metastases tissue.
Abbreviations: P, primary tumor; M, metastases.
See this image and copyright information in PMC

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