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

• Published in: Clinical cancer research 2003-10, Vol.9 (13), p.4872-4876
• Main Authors: POTTI, Anil, APAR KISHOR GANTI, SHOLES, Kaley, LANGNESS, Eric, KOKA, Vijay, HORVARTH, Linda, KOCH, Michael
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinoma, Small Cell - chemically induced; Carcinoma, Small Cell - metabolism; Cell Line, Tumor; Female; Humans; Immunohistochemistry; Lung Neoplasms - chemically induced; Lung Neoplasms - metabolism; Male; Medical sciences; Middle Aged; Odds Ratio; Pesticides - adverse effects; Pneumology; Receptor, ErbB-2 - biosynthesis; Retrospective Studies; Surveys and Questionnaires; Time Factors; Tumors of the respiratory system and mediastinum
• ISSN: 1078-0432; 1557-3265

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 × days/year × 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.