title: Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatin.
abstract: Increased expression of thymidylate synthase (TS) is thought to be associated with resistance to antifolate drugs such as pemetrexed. Excision repair cross-complementation group 1 (ERCC1) is a predictive marker for platinum-based chemotherapy. This study evaluated whether the expression of TS and ERCC1 proteins is associated with clinical outcomes of the patients with pulmonary adenocarcinoma who were treated with pemetrexed/cisplatin as first-line chemotherapy. The expressions of TS and ERCC1 were evaluated by immunohistochemistry in biopsy specimens obtained from patients with pulmonary adenocarcinoma who had received pemetrexed/cisplatin as first-line treatment. Patients were categorized according to median H-score. Response rate (RR), progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively. Both low TS and ERCC1 expressions were significantly associated with better RR (p = 0.037 and p = 0.015, respectively) and longer PFS (p < 0.001 and p = 0.004, respectively). Low ERCC1 expression was also associated with longer OS (p = 0.003) while TS only showed a trend (p = 0.105). TS expression was independent predictor for the better PFS in multivariate analysis (hazard ratio [HR] = 0.32, 95% confidence interval [CI]: 0.14-0.76). Combining the two markers, the low TS/low ERCC1 group showed significantly longer PFS (HR = 0.48, 95% CI: 0.26-0.75) and OS (HR = 0.57, 95% CI: 0.36-0.89) compared with high TS/high ERCC1 group. Protein expressions of TS and ERCC1 were associated with clinical outcomes in patients with pulmonary adenocarcinoma who were treated with pemetrexed/cisplatin as first-line chemotherapy. TS and ERCC1 protein expressions can be potential predictive markers in this setting.
authors.affiliation: Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Korea University, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Republic of Korea. humanmd04@hanmail.net
authors.forename: Seung Hyeun
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyung Bo
authors.initials: KB
authors.lastname: Noh
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Gyu Young
authors.initials: GY
authors.lastname: Hur
authors.forename: Seung Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.forename: Sang Yeub
authors.initials: SY
authors.lastname: Lee
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Shim
authors.forename: Chul Hwan
authors.initials: CH
authors.lastname: Kim
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Kang
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: In
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D016001:Confidence Intervals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin