title: High RRM1 Expression Is Associated with Adverse Outcome in Patients with Cisplatin/Vinorelbine-treated Malignant Pleural Mesothelioma.
abstract: OBJECTIVE
  A possible predictive impact of ribonucleotide-reductase subunit-1 (RRM1) on vinorelbine efficacy in non-small cell lung cancer (NSCLC) has been previously reported. The present study aimed to further explore this finding in malignant pleural mesothelioma (MPM).
  
  
  METHODS
  Seventy-one patients with MPM receiving first-line chemotherapy with cisplatin-vinorelbine (CiV group, n=54) or carboplatin-pemetrexed (CaP group, n=17) were included. Formalin-fixed paraffin-embedded tumor specimens were analyzed by immunohistochemistry (IHC) for RRM1 expression using an H-score.
  
  
  RESULTS
  In 66 patients eligible for IHC, the H-score was ≥upper quartile in 21 (RRM1-positive) and <upper quartile (RRM1-negative) in 45 cases. The long-term (2-year) survival rate for patients with RRM1-negative MPM in the CiV-treated group was significantly superior to that for patients with RRM1-positive MPM (47% versus 13%, p=0.002). No difference occurred in the CaP-treated group.
  
  
  CONCLUSIONS
  Our findings suggest a possible role of RRM1 in predicting efficacy of cisplatin-vinorelbine in MPM, supporting previous findings in NSCLC.
authors.affiliation: Department of Oncology, Finsen Centre/National University Hospital, Copenhagen, Denmark.
authors.forename: Zarah Glad
authors.initials: ZG
authors.lastname: Zimling
authors.affiliation: Department of Pathology, National University Hospital, Copenhagen, Denmark.
authors.forename: Eric
authors.initials: E
authors.lastname: Santoni-Rugiu
authors.affiliation: Department of Oncology, Finsen Centre/National University Hospital, Copenhagen, Denmark.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bech
authors.affiliation: Department of Oncology, Finsen Centre/National University Hospital, Copenhagen, Denmark jens.benn.soerensen@regionh.dk.
authors.forename: Jens Benn
authors.initials: JB
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D012262:Ribonucleoside Diphosphate Reductase; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D014747:Vinblastine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Biomarkers; chemotherapy; malignant mesothelioma; vinorelbine