title: Platinum-based chemotherapy in lung cancer affects the expression of certain biomarkers including ERCC1.
abstract: Chemotherapies are widely used in the treatment of lung cancer. However, little is known about their effect in the expression of different tissue markers. Seventeen lung cancer tissue blocks obtained by bronchoscopic biopsies together with their corresponding surgical biopsies after neoadjuvant chemotherapy were studied. They included 9 adenocarcinomas (ADC) and 8 squamous cell carcinomas (SCC). Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues to study the expression of Ki-67, p53, Bcl-2, Bax, Fas-ligand and ERCC1 (excision repair cross-complementation group 1). Out of 17 NSCLC 6 expressed proapoptotic markers and 4 expressed antiapoptotic markers, while in 7 cases the apoptotic markers did not show detectable changes after neoadjuvant chemotherapy. Six of 17 bronchoscopic NSCLC cases expressed increased level of Ki-67 after neoadjuvant treatment. Eight bronchoscopic NSCLC tissues (6 SCC, 2 ADC) expressed ERCC1. All but one ADC became ERCC1 negative after neoadjuvant therapy. There was no newly expressed ERCC1 positive case in the surgical biopsy group. Platinum-based neoadjuvant chemotherapy had no effect on the apoptotic activity of 17 patients' tumor specimen, however, 6 of 17 bronchoscopic NSCLC cases expressed increased level of Ki-67 after neoadjuvant treatment, in 3 cases the level of Ki-67 became decreased, while 8 cases had no detectable change of proliferation activity. The results of the present study suggest that platinum-based chemotherapy probably induces a selection of tumor cells with more aggressive phenotype, and also affects the expression of tissue marker (ERCC1) that could have predictive value.
authors.affiliation: I. Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Pápay
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Sápi
authors.forename: Gábor
authors.initials: G
authors.lastname: Egri
authors.forename: Márton
authors.initials: M
authors.lastname: Gyulai
authors.forename: Béla
authors.initials: B
authors.lastname: Szende
authors.forename: György
authors.initials: G
authors.lastname: Losonczy
authors.forename: József
authors.initials: J
authors.lastname: Tímár
authors.forename: Judit
authors.initials: J
authors.lastname: Moldvay
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000187:drug effects; D004720:Endonucleases / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017671:Platinum Compounds / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D017671:Platinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases