title: Decreased ERCC1 Expression After Platinum-Based Neoadjuvant Chemotherapy in non-Small Cell Lung Cancer.
abstract: We have already demonstrated in a small cohort of 17 non-small cell lung cancer patients that ERCC1 (excision repair cross-complementation group 1) protein expression decreased after platinum-based treatment, however, certain clinicopathological parameters, such as histologic subtypes, ERCC1 expression scores, chemotherapeutic combinations, response rate, gender and smoking history were not analyzed. The aim of our present study was to extend the studied cohort and analyze those parameters. ERCC1 protein expression was examined in 46 patients treated with neoadjuvant chemotherapy. 46 bronchoscopic biopsy samples (27 squamous cell carcinomas /SCC/ and 19 adenocarcinomas /ADC/) together with their corresponding surgical biopsies were studied. ERCC1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. Staining scores were calculated by multiplying the percentage of positive tumor cells (0-100) by the staining intensity (0-3). 24/27 bronchoscopic SCC tissues expressed ERCC1. Thirteen of these cases became negative after neoadjuvant therapy and the expression differences between pre- and postchemotherapy samples were highly significant (p < 0.001). 11/19 bronchoscopic ADC tissues expressed ERCC1. Six of these cases became negative after neoadjuvant therapy and the expression differences were significant (p < 0.010). There was no newly expressed ERCC1 postoperatively. Comparison of staining score changes revealed more pronounced decrease in SCC (p = 0.032). We observed no correlation between initial ERCC1 level or ERCC1 decrease and overall survival, but we demonstrated correlations between decrease in ERCC1 expression and histologic subtypes of tumors and gender. We could confirm our previous data in a larger cohort that platinum-based chemotherapy affects the ERCC1 expression probably referring to an induction of tumor cell selection.
authors.affiliation: Department of Pulmonology, Semmelweis University, Diosarok u. 1/c, Budapest, H-1125, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Podmaniczky
authors.forename: Katalin
authors.initials: K
authors.lastname: Fábián
authors.forename: Judit
authors.initials: J
authors.lastname: Pápay
authors.forename: Rita
authors.initials: R
authors.lastname: Puskás
authors.forename: Márton
authors.initials: M
authors.lastname: Gyulai
authors.forename: József
authors.initials: J
authors.lastname: Furák
authors.forename: László
authors.initials: L
authors.lastname: Tiszlavicz
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: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010984:Platinum / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D010984:Platinum; C071447:ERCC1 protein, human; D004720:Endonucleases