title: EGFR, BRAF and KRAS status in patients undergoing pulmonary metastasectomy from primary colorectal carcinoma: a prospective follow-up study.
abstract: BACKGROUND
  Pulmonary metastasectomy is an integral part of the interdisciplinary treatment of patients with pulmonary metastases (PMs) from colorectal carcinoma (CRC). Although alterations in the epidermal growth factor receptor (EGFR) pathway are common in CRC, there is still insufficient data regarding PM. We hypothesized that EGFR expression and Kirsten rat sarcoma viral oncogene homolog (KRAS)/BRAF mutations (Mts) might be associated with clinicopathological variables and the outcome in patients undergoing pulmonary metastasectomy.
  
  
  METHODS
  In this single-center study, 44 patients undergoing pulmonary metastasectomy from primary CRC were included and prospectively followed up. Tissue specimens of resected PMs were assessed. Restriction fragment length analysis was used for BRAF V600E and KRAS codons 12 and 13 Mt analyses. EGFR expression was evaluated by immunohistochemistry. Patients were followed up in 3-6-month intervals.
  
  
  RESULTS
  EGFR expression was evident in 49 % of the PMs, whereas Mts in KRAS and BRAF were detected in 48 and 0 %, respectively. Time to lung-specific recurrence after metastasectomy was significantly decreased in patients with KRAS mutated PMs in univariate (p = 0.013) and multivariate analysis (p = 0.035), whereas EGFR expression had no impact on recurrence free survival. Moreover, KRAS Mts were associated with the number of PMs (p = 0.037) and with the lung as first site of recurrence after metastasectomy (p = 0.047).
  
  
  CONCLUSIONS
  This is the first evaluation of EGFR pathway alterations in the setting of pulmonary metastasectomy. Our data suggest that patients with KRAS Mts are at high risk for early pulmonary recurrence and have a more diffuse pattern of metastasis. These findings may have impact on the therapeutic management of CRC patients with pulmonary spreading.
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schweiger
authors.forename: Balazs
authors.initials: B
authors.lastname: Hegedüs
authors.forename: Christoph
authors.initials: C
authors.lastname: Nikolowsky
authors.forename: Zita
authors.initials: Z
authors.lastname: Hegedüs
authors.forename: Ildiko
authors.initials: I
authors.lastname: Szirtes
authors.forename: Roland
authors.initials: R
authors.lastname: Mair
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Balazs
authors.initials: B
authors.lastname: Döme
authors.forename: György
authors.initials: G
authors.lastname: Lang
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008297:Male; D059146:Metastasectomy; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins