title: Combined evaluation of Rad51 and ERCC1 expressions for sensitivity to platinum agents in non-small cell lung cancer.
abstract: DNA repair enzyme expression in tumor cells possibly affects sensitivity to anti-cancer agents. The aim of this study was to determine the relationship between expression status of DNA repair enzymes and chemosensitivity in patients with non-small cell lung cancer (NSCLC). NSCLC tissues prepared from the surgical specimens of 41 patients were subjected to immunohistochemical analysis for Rad51 and ERCC1 proteins and to a chemosensitivity test using the MTT assay. The relationships between the expression status of the DNA repair enzymes and ex vivo chemosensitivity to various agents were evaluated. A positive expression for Rad51 and ERCC1 was observed in 17 cases (41%) and 20 cases (49%), respectively. The positivity of Rad51 was closely related to a certain histologic type of squamous cell carcinoma and poor differentiation, and the positivity of ERCC1 tended to be related to squamous cell carcinoma. In chemosensitivity tests, sensitivities to CDDP and CBDCA were significantly lower when both 2 enzymes were positive (p = 0.012 and 0.04 in CDDP, 0.014 and 0.03 in CBDCA). Both Rad51 and ERCC1 expressions showed no significant relationship with sensitivities to paclitaxel, etoposide, vinorelbine, gemcitabine, 5-FU, or irinotecan. In conclusion, combined expression of Rad51 and ERCC1 expression is associated with resistance to platinum agents in the ex vivo study of clinical NSCLC, and evaluation of expression status of both DNA repair enzymes would be a predictor for clinical response to platinum-based chemotherapies.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Takenaka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kouso
authors.forename: Taro
authors.initials: T
authors.lastname: Ohba
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Yohena
authors.forename: Atsushi
authors.initials: A
authors.lastname: Osoegawa
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Shoji
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000627:therapeutic use*; D051135:Rad51 Recombinase / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D017671:Platinum Compounds; D051135:Rad51 Recombinase; C071447:ERCC1 protein, human; D004720:Endonucleases