Concordant analysis of KRAS, BRAF, PIK3CA mutations and PTEN expression between primary colorectal cancer and matched metastases
Open accessAbstract
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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Analysis of circulating tumor DNA (ctDNA) from patients with KRAS wild-type tumors who received anti-EGFR antibody therapy revealed that 38% of these cases exhibited mutant KRAS, suggesting the clonal selection of mutant cells within metastatic lesions.
“an analysis of circulating tumor DNA (ctDNA) from patients with KRAS wild-type tumors who received anti-EGFR antibody therapy revealed that 38% of these cases exhibited mutant KRAS, suggesting the clonal selection of mutant cells within metastatic lesions [58]”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [58]
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- Authors
- Mao, C., Wu, X.-Y., Yang, Z.-Y., Threapleton, D. E., Yuan, J.-Q., Yu, Y.-Y., & Tang, J.-L.
- Affiliations
- Chinese University of Hong Kong (HK)
- Venue
- Scientific Reports
- Published
- 2015-02-02
- Volume
- 5
- Issue
- 1
- Pages
- 8065-8065
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4648436
- OpenAlex
- W2011847340
- Cited by
- 107
- References
- 55
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 9 · 2018: 11 · 2017: 19 · 2016: 16 · 2015: 7
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Chinese University of Hong Kong
- Food and Health Bureau
- Health and Medical Research Fund (12130721, 11120971)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal cancer, KRAS mutation, BRAF mutation, PIK3CA mutation, PTEN expression, primary tumor versus metastasis concordance, tumor markers, anti-EGFR therapy, false positive and false negative rates
- MeSH terms
- Humans, Liver Neoplasms, Lymph Nodes, Lymphatic Metastasis, Mutation, Biomarkers, Tumor, Colorectal Neoplasms, Databases, Factual, ras Proteins, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins B-raf, PTEN Phosphohydrolase, Class I Phosphatidylinositol 3-Kinases
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