title: Thymidylate synthase protein expression levels remain stable during paclitaxel and carboplatin treatment in non-small cell lung cancer.
abstract: BACKGROUND
  Thymidylate synthase (TS) is a potential predictive marker for efficacy of treatment with pemetrexed. The current study aimed at investigating whether TS expression changes during non-pemetrexed chemotherapy of non-small cell lung cancer (NSCLC), thus making rebiopsy necessary for deciding on pemetrexed second-line treatment.
  
  
  METHODS
  TS immunohistochemístry was performed on biopsies and available resection specimens from 65 NSCLC patients stage T1-3N0-2 treated with preoperative carboplatin and paclitaxel [neoadjuvant chemotherapy (NAC)-group] and from 53 NSCLC patients stage T1-4N0-1 treated with surgery without preceding chemotherapy [operation (OP)-group] that served as controls. The diagnostic biopsies and subsequent resection samples were compared in order to evaluate for change in TS expression in groups treated with and without preoperative chemotherapy.
  
  
  RESULTS
  No statistically significant change in TS expression was observed between diagnostic biopsies and subsequent surgical resections of primary tumors in either the OP-group (p = 0.186) or the NAC-group (p = 0.542). Primary tumors were discordant between diagnostic biopsies and resection specimens when TS expression was dichotomized into high (H score ≥ 150) and low (H score < 150), in 45 and 33% in the OP-group and NAC-group, respectively (p = 0.288). The fraction of tumors which increased (19 vs. 20%; p = 0.900) and decreased (42 vs. 23%; p = 0.095) in TS expression was equal between the OP- and the NAC-group.
  
  
  CONCLUSIONS
  The discordance observed between paired serial samples likely reflects intratumoral heterogeneity of TS expression and highlights the need of sufficient representative material for TS expression analysis if this biomarker is to be used for treatment selection. TS expression in primary tumors remained unchanged, and new biopsies for deciding on second-line pemetrexed does not seem warranted based on the current results.
authors.affiliation: Department of Oncology, Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen, Denmark, jan.nyrop.jakobsen@rh.regionh.dk.
authors.forename: Jan Nyrop
authors.initials: JN
authors.lastname: Jakobsen
authors.forename: Eric
authors.initials: E
authors.lastname: Santoni-Rugiu
authors.forename: Jens Benn
authors.initials: JB
authors.lastname: Sørensen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D016190:Carboplatin; D013940:Thymidylate Synthase; D017239:Paclitaxel