[Comparison of EGFR and KRAS status between primary non-small cell lung cancer and corresponding metastases: a systematic review and meta-analysis].
OBJECTIVE
Epidermal growth factor receptor (EGFR) and KRAS status were particularly critical for the choice of first-line targeted therapy of non-small cell lung cancer (NSCLC), while the primary tumor and metastases might be different in the EGFR and KRAS gene status. The aim of this pooled analysis is to compare EGFR and KRAS status in matching primary NSCLC and metastases and further to guide clinical practice.


METHODS
Systematic computerized searches of the Pubmed and Medline databases (up to May 10, 2010) meeting specified search criteria were performed, followed by a further screening according to inclusive and exclusive criteria.


RESULTS
Fourteen articles were selected into the final meta-analysis with paired primary and metastatic cases of 598. Expression level of EGFR protein and mutation frequency of KRAS gene in primary tumors were higher than that in metastases, relative risk (RR)=1.13 (95%CI: 0.98-1.31, P=0.09) and RR=1.39 (95%CI: 0.95-2.03, P=0.09), respectively. EGFR gene copy number in metastases was higher than that in primary tumor, RR=0.74 (95%CI: 0.53-1.02, P=0.06). There was no statistically significant difference of EGFR mutation frequency in primary tumors and metastases (P=0.31). The discordant rate in primary and metastases was 17.09% for EGFR mutation, 27.07% for EGFR amplification, 27.84% for EGFR protein expression and 25.91% for KRAS mutation.


CONCLUSIONS
The systematic analysis showed that the EGFR mutation status in primary lung cancer and corresponding metastases was more stable than KRAS gene. KRAS mutation in primary lung cancerous foci seems to better reflect systemically cancerous genetic characteristics of KRAS gene. Determination of KRAS gene status based merely on metastatic foci might lead to more resistant selections of EGFR tyrosine kinase inhibitor (TKI) therapy. Combined detection of EGFR and KRAS mutation from primary NSCLC foci might serve as a better predictive biomarker for anti-EGFR targeted therapy.
Han
Chengbo
C
Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110022, China. hancb@126.com
Zou
Huawei
H
Ma
Jietao
J
Zhou
Yang
Y
Zhao
Jianzhu
J
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009154:Mutation; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins