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Effect of Pesticide Exposure on HER-2/neu Overexpression Seen in Patients with Extensive Stage Small Cell Lung Carcinoma

Department of Medicine, University of North Dakota School of Medicine, Fargo, North Dakota 58102 [A. P., A. K. G., K. S., E. L., V. K.], and Department of Pathology [M. K.], Division of Oncology, Veterans’ Affairs Medical Center [L. H.], Fargo, North Dakota 58102

Purpose: The aim of this study was to evaluate the relationship, if any, between pesticide exposure and overexpression of the HER-2/neu oncoprotein in extensive stage small cell lung cancer (ESSCLC).

Experimental Design: The records of all patients with a diagnosis of ESSCLC from January 1991 through April 2001 were reviewed in our retrospective study. Pesticide risk (herbicide and insecticide) was assessed by telephone interviews using a predetermined questionnaire with emphasis on type of exposure, use of protective measures, and duration of exposure. An exposure index was calculated (h/day x days/year x years), and patients with an index > 2400 h were considered as exposed. HER-2/neu overexpression was assessed by immunohistochemistry using the Hercep test developed by Dako. Statistical analysis was performed using SPSS-10.

Results: A total of 193 patients (84 females and 109 males), with a mean age of 68.5 years (range, 42–90 years) were included in the study. Of these, 57 (29.5%) revealed HER-2/neu overexpression by immunohistochemistry. After adjusting for age, smoking, Eastern Cooperative Oncology Group score, and treatment, HER-2/neu overexpression was associated with a statistically significant diminished survival (P < 0.001; Mann-Whitney U test). We contacted 53 of 57 patients with overexpression and 121 of 136 patients without HER-2/neu overexpression to ascertain a history of pesticide exposure. Forty-one of 53 (77.4%) patients with HER-2/neu overexpression and 47 of the 121 patients without overexpression (38.8%) were exposed to pesticides. We found that patients with history of pesticide exposure had a higher risk of having HER-2/neu overexpression (odds ratio, 5.38; P < 0.01, 95% confidence interval, 2.5–11.2)

Conclusions: HER-2/neu is overexpressed in 30% patients with ESSCLC and is associated with decreased survival. Also, pesticide exposure seems to be related to HER-2/neu overexpression seen in our patient population. Future studies are needed to validate our findings and also to determine which pesticide(s)/pesticide components are actually responsible for HER-2/neu overexpression seen in ESSCLC.