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Abstract

BackgroundThe 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.MethodsTo 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 × days/year × years) ≥ 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).Results193 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).ConclusionPesticide 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.

Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation

“…5b: p1∼3). The expression of CD117 and Sca-1 may signify the malignancy of the Lin + cells, because CD117, a transmembrane tyrosine kinase receptor encoded by proto-oncogene c-kit, and Sca-1, a glycosylphosphatiylinositol-linked cell surface protein, have been identified as markers of cancer progression in various types of cancer [31]–[33]. Based on the results (Fig.…”

Pesticides and Bladder Cancer: Mechanisms Leading to Anti-Cancer Drug Chemoresistance and New Chemosensitization Strategies

“…RC48-ADC (disitamab vedotin), conjugating the anti-HER2 antibody hertuzumab to MMAE, had activity in BlCa patients with HER2-amplified or mutated failing chemotherapy [198]. As increased HER2 expression has been found to be correlated with pesticide exposure, this may prove to be an effective therapeutic approach [199]. HER2 is a member of the epidermal growth factor receptor (EGFR) family and class I evidence revealed that DMA elevated EGFR activation in rat urothelial cells, and that the EGFR inhibitor gefitinib blocked DMA-induced cell proliferation in vitro as well as in the rat urothelium [200].…”

The Efficacy and Safety of Anlotinib Plus Etoposide with Cisplatin/Carboplatin in the First-Line Treatment of Lung Cancer: A Phase II Clinical Study

“…In comparison to several other types of lung cancer, chemotherapy and radiotherapy are less effective for treating SCLC 7 - 10 . However, due to the widespread distribution of SCLC at the time of diagnosis, achieving a cure is often challenging 11 , 12 . Various techniques utilizing artificial intelligence or CT scans may efficiently and promptly detect this form of lung cancer 13 - 16 .…”