title: Concordant analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression between primary colorectal cancer and matched metastases.
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.
authors: 1] Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong [2] The Hong Kong Branch of The Chinese Cochrane Centre, The Chinese University of Hong Kong, Hong Kong [3] Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of The Chinese University of Hong Kong, Shenzhen, Guangdong Province, China.
authors: Chen
authors: C
authors: Mao
authors: Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
authors: Xin-Yin
authors: XY
authors: Wu
authors: Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
authors: Zu-Yao
authors: ZY
authors: Yang
authors: Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
authors: Diane Erin
authors: DE
authors: Threapleton
authors: Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
authors: Jin-Qiu
authors: JQ
authors: Yuan
authors: Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
authors: Yuan-Yuan
authors: YY
authors: Yu
authors: 1] Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong [2] The Hong Kong Branch of The Chinese Cochrane Centre, The Chinese University of Hong Kong, Hong Kong [3] Shenzhen Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of The Chinese University of Hong Kong, Shenzhen, Guangdong Province, China.
authors: Jin-Ling
authors: JL
authors: Tang
mesh_terms: D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016208:Databases, Factual; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000235:genetics; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D018631:ras Proteins
references: Int J Cancer. 1991 Dec 2;49(6):875-9
references: 1959991
references: Mol Pathol. 2003 Jun;56(3):137-40
references: 12782759
references: Eur J Cancer. 1992;28A(6-7):1115-20
references: 1627381
references: Oncol Lett. 2014 Oct;8(4):1422-1426
references: 25202344
references: J Clin Oncol. 2010 Mar 1;28(7):1254-61
references: 20100961
references: Int J Cancer. 1992 Aug 19;52(1):30-3
references: 1500224
references: Dis Colon Rectum. 2000 Feb;43(2):155-9; discussion 159-62
references: 10696887
references: Ann Oncol. 2009 May;20(5):879-84
references: 19179548
references: Clin Cancer Res. 2010 Feb 1;16(3):790-9
references: 20103678
references: Oncogene. 2007 Jan 4;26(1):158-63
references: 16953233
references: Cancer Res. 1999 Oct 15;59(20):5169-75
references: 10537293
references: Ann Oncol. 2009 Jan;20(1):84-90
references: 18669866
references: Int J Cancer. 2013 Jul;133(1):130-41
references: 23233388
references: Oncologist. 2008 Dec;13(12):1270-5
references: 19056857
references: Ann Intern Med. 2011 Oct 18;155(8):529-36
references: 22007046
references: Int J Clin Oncol. 2014 Feb;19(1):113-20
references: 23299277
references: Curr Cancer Drug Targets. 2012 Feb;12(2):124-31
references: 22229245
references: Cancer. 1993 Jun 15;71(12):3827-38
references: 8508351
references: Br J Cancer. 2011 Mar 15;104(6):1020-6
references: 21364579
references: Oncologist. 2011;16(9):1239-49
references: 21742964
references: Mod Pathol. 2013 Feb;26(2):302-13
references: 22936063
references: Cancer Chemother Pharmacol. 2010 Aug;66(3):605-9
references: 20361188
references: J Clin Oncol. 2012 Aug 20;30(24):2956-62
references: 22665543
references: Nature. 2002 Aug 29;418(6901):934
references: 12198537
references: BMJ. 2007 Oct 20;335(7624):806-8
references: 17947786
references: Br J Cancer. 2012 Jul 10;107(2):340-4
references: 22617127
references: J Clin Oncol. 2009 Jun 1;27(16):2622-9
references: 19398573
references: Ann Oncol. 2010 Jul;21(7):1565
references: 20573852
references: N Engl J Med. 2013 Sep 12;369(11):1023-34
references: 24024839
references: Ann Surg Oncol. 2010 May;17(5):1429-34
references: 20049644
references: Br J Cancer. 2013 Jul 23;109(2):408-15
references: 23764749
references: Dis Colon Rectum. 2011 Sep;54(9):1170-8
references: 21825899
references: Anticancer Res. 2010 Oct;30(10):4229-35
references: 21036746
references: PLoS One. 2009;4(12):e8199
references: 20020061
references: Clin Cancer Res. 2011 Mar 1;17(5):1122-30
references: 21239505
references: Biochem Biophys Res Commun. 2004 Dec 17;325(3):784-91
references: 15541358
references: J Pathol. 1998 Jun;185(2):130-8
references: 9713338
references: Clin Cancer Res. 2008 Aug 1;14(15):4830-5
references: 18676755
references: Int J Cancer. 2007 Feb 1;120(3):524-32
references: 17096353
references: J Clin Pathol. 2012 May;65(5):466-9
references: 22259183
references: Lancet Oncol. 2005 May;6(5):279-86
references: 15863375
references: N Engl J Med. 2009 Apr 2;360(14):1408-17
references: 19339720
references: Cancer Med. 2013 Aug;2(4):496-506
references: 24156022
references: Cancer Chemother Pharmacol. 2011 Oct;68(4):1045-55
references: 21340604
references: Br J Cancer. 2009 Apr 7;100(7):1087-94
references: 19293803
references: BMC Cancer. 2012;12:347
references: 22876814
references: J Clin Oncol. 2008 Sep 1;26(25):4217-9
references: 18757341
references: Br J Cancer. 2010 Jan 5;102(1):162-4
references: 19953097
references: Clin Cancer Res. 2012 Feb 1;18(3):688-99
references: 22173549
references: Pathol Res Pract. 2013 Apr;209(4):233-6
references: 23538047