HER-2/neu and CD117 (c-kit) overexpression in patients with pesticide exposure and extensive stage small cell lung carcinoma (ESSCLC)

BACKGROUND The rate of detection of HER-2/neu and CD117 (c-kit) overexpression in small cell lung cancer (SCLC) has varied widely; between 5-35% and 21-70% respectively. METHODS To evaluate the relationship between pesticide exposure and HER-2/neu and CD117 overexpression in extensive stage SCLC (ESSCLC), we identified patients with ESSCLC and assessed pesticide exposure using a predetermined questionnaire. An exposure index (hours/day x days/year x years) > or = 2400 hours was considered as 'exposed.' HER-2/neu overexpression was evaluated on archival tissue using the DAKO Hercep test, and CD117 testing was performed using immunohistochemistry (A4052 polyclonal antibody). RESULTS 193 ESSCLC patients were identified. Pesticide exposure data could be obtained on 174 patients (84 females and 109 males) with a mean age of 68.5 years. 53/174 (30.4%) revealed HER-2/neu overexpression. 54/174 (31.03%) specimens showed CD117 overexpression by IHC. On multivariate analysis, HER-2/neu overexpression was associated with diminished survival (p < 0.001). In comparison, CD117 expression did not have an adverse prognostic value (p = 0.025). 41/53 (77.4%) patients with HER-2/neu overexpression and 47/121 (38.8%) patients without overexpression had exposure to pesticides (odds ratio: 5.38; p < 0.01). Among the cohort tested for CD117, 29/54 (53.7%) patients with CD117 overexpression and 59/120 (49.2%) patients without CD117 overexpression had pesticide exposure (odds ratio: 1.18; p = 0.12). CONCLUSION Pesticide exposure affects HER-2/neu but not CD117 overexpression. Future studies are needed to determine specific pesticide(s)/pesticide components that are responsible for HER-2/neu overexpression in ESSCLC, and to validate our findings in other solid tumors that overexpress HER-2/neu.