title: Synchronous overexpression of epidermal growth factor receptor and HER2-neu protein is a predictor of poor outcome in patients with stage I non-small cell lung cancer.
abstract: OBJECTIVE
  Despite maximal therapy, surgically treated patients with stage I non-small cell lung cancer (NSCLC) are at risk for developing metastatic disease. Histopathologic findings cannot adequately predict disease progression, so there is a need to identify molecular factors that serve this purpose. Because the ErbB receptors play an important role in lung cancer progression, we analyzed the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, transforming growth factor alpha (TGFalpha), and HER2-neu as potential prognostic factors in stage I NSCLC.
  
  
  METHODS
  Using immunohistochemical techniques, we retrospectively analyzed formalin-fixed, paraffin-embedded samples from 111 patients with resected pathological stage I NSCLC. Then we correlated these data with patient clinical outcome.
  
  
  RESULTS
  Median follow-up was 69.3 months. EGFR overexpression (defined as >10% membranous staining) was found in 66 tumors (59.5%). It was significantly more common in T(2) tumors than in T(1) tumors (P = 0.001), and in more squamous cell carcinomas than in adenocarcinomas (P = 0.07). HER2-neu overexpression was found in 19 tumors (17.1%) and was significantly more common in adenocarcinomas than in squamous cell carcinomas (P = 0.035). Synchronous overexpression of EGFR and HER2-neu was found in 11 tumors (9.9%). Patients with these tumors had a significantly shorter time to recurrence (P = 0.006) and a trend toward shorter overall survival (P = 0.093). Phosphorylated EGFR and transforming growth factor alpha were detected but were not related to prognosis.
  
  
  CONCLUSIONS
  Synchronous overexpression of EGFR and HER2-neu at the protein level predicts increased recurrence risk and may predict decreased survival in patients with stage I NSCLC. This suggests that important interactions take place among the different members of the ErbB family during tumor development and suggests a method for choosing targeted therapy. A prospective study is planned.
authors.affiliation: Department of Thoracic, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Onn
authors.forename: Arlene M
authors.initials: AM
authors.lastname: Correa
authors.forename: Michael
authors.initials: M
authors.lastname: Gilcrease
authors.forename: Takeshi
authors.initials: T
authors.lastname: Isobe
authors.forename: Erminia
authors.initials: E
authors.lastname: Massarelli
authors.forename: Corazon D
authors.initials: CD
authors.lastname: Bucana
authors.forename: Michael S
authors.initials: MS
authors.lastname: O'Reilly
authors.forename: Waun K
authors.initials: WK
authors.lastname: Hong
authors.forename: Isaiah J
authors.initials: IJ
authors.lastname: Fidler
authors.forename: Joe B
authors.initials: JB
authors.lastname: Putnam
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000175:diagnosis / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism*; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016211:Transforming Growth Factor alpha / Q000378:metabolism
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha