title: KRAS discordance between primary and metastatic tumor in patients with metastatic colorectal carcinoma.
abstract: OBJECTIVE
  Adding targeted therapies to chemotherapy in metastatic colorectal cancer (CRC) improves response rates and survival. KRAS is a predictive indicator for anti-epidermal growth factor receptor (EGFR) treatments. The most important reasons for KRAS discordance are intratumoral heterogeneity and incorrect mutation analysis. Evaluating the status of KRAS in primary and metastatic lesions becomes even more crucial to ensure efficient usage of anti-EGFR treatments.
  
  
  METHODS
  Patients with metastatic CRC, whose primary disease and liver and/or lung metastases were operated, were retrospectively evaluated, and KRAS assessment was performed on 31 patients who were suitable for DNA analysis. Pyrosequencing with polymerase chain reaction (PCR) was used for KRAS analysis.
  
  
  RESULTS
  The median age of 31 patients diagnosed with rectal cancer (N=13) and colon cancer (N=18) was 63 years (range 33-73). Metastasectomy locations included the liver (N=27), lung (N=3), and both lung and liver (N=1). KRAS discordance was detected in 22% (7/31) of the patients. While 3 patients with detected discordance had mutated KRAS in the primary material, wild type KRAS was detected in their liver or lung lesions. On the other hand, while 4 patients had wild type KRAS in the primary material, mutated KRAS was determined in their liver or lung lesions. The McNemar test revealed no significant discordance between primary and metastatic disease (p=1.00). No progression free survival (PFS) difference was detected between patients with determined discordance and patients with undetermined discordance (10.6 vs 14.7 months, p=0.719).
  
  
  CONCLUSIONS
  This is the first study to evaluate KRAS discordance between primary and metastasis in CRC patients, who underwent metastasectomy, together with survival data. In the literature and recent studies with large patient numbers in which modern KRAS tests were used, the KRAS discordance rate varies between 3-12%. In our study, a higher KRAS discordance (22%) was detected, and no survival difference was determined between patients with or without discordance. In recent years, the rising interest in borderline resectable disease may bring forward discussions related to which material the KRAS status should be analyzed.
authors.affiliation: 1Dr.Abdurahman Yurtarslan Oncology Hospital, Department of Medical Oncology, Ankara, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Siyar Ekinci
authors.forename: Umut
authors.initials: U
authors.lastname: Demirci
authors.forename: Berna
authors.initials: B
authors.lastname: Cakmak Oksuzoglu
authors.forename: Ayse
authors.initials: A
authors.lastname: Ozturk
authors.forename: Onur
authors.initials: O
authors.lastname: Esbah
authors.forename: Tahsin
authors.initials: T
authors.lastname: Ozatli
authors.forename: Burcin
authors.initials: B
authors.lastname: Celik
authors.forename: Burcin
authors.initials: B
authors.lastname: Budakoglu
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Turker
authors.forename: Oznur
authors.initials: O
authors.lastname: Bal
authors.forename: Nedim
authors.initials: N
authors.lastname: Turan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D008297:Male; D059146:Metastasectomy / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011013:Pneumonectomy; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins