title: [The importance of p53 and ras mutation as predictive markers for adjuvant chemotherapy in non-small-cell lung cancer].
abstract: OBJECTIVE
  A previous large, randomized, control trial(JBR.10)revealed that adjuvant chemotherapy with cisplatin(CDDP) and vinorelbine(VNR)was effective for non-small-cell lung cancer(NSCLC). It was also reported that adjuvant chemotherapy was not effective for p53-negative or K-ras mutation-positive patients. To clarify whether p53 and ras statuses are true predictive markers for chemotherapy with cisplatin, chemosensitivity was examined using an in vitro drug sensitivity assay.
  
  
  METHODS
  Surgically resected fresh tumor specimens obtained from 27 patients at our institute with NSCLC were used for this study. Histoculture Drug Response Assay(HDRA)was applied to evaluate the chemosensitivity of CDDP and VNR in these specimens. p53 expression was evaluated by immunohistochemistry, and K-ras mutation by direct sequencing.
  
  
  RESULTS
  Four of the 27 patients were positive for K-ras mutation. The inhibition rate of CDDP was 54±5% for K-ras mutation positive-patients, and 50±13% for negative-patients. There was no significant difference between these two groups. p53 overexpression was observed in 14 patients, but not in 13 patients. The inhibition rate of CDDP was 50±12% for p53- overexpressed patients, and 50±12% for patients not overexpressed. The inhibition rate of VNR was 36±17% for p53- overexpressed patients, and 33±14%for patients not overexpressed. As for 8 adenocarcinoma patients, the inhibition rate of CDDP of p53-overexpressed patients(59±8%)was significantly(p=0. 018)higher than that of patients not overexpressed (45±9%). p53 overexpression may be a predictive marker for chemotherapy using CDDP in lung adenocarcinoma.
  
  
  CONCLUSIONS
  p53 overexpression may be a possible predictive marker for adjuvant chemotherapy using CDDP in NSCLC.
authors.affiliation: Dept. of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Hirai
authors.forename: Yukio
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Shoji
authors.initials: S
authors.lastname: Oura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshimasu
authors.forename: Fuminori
authors.initials: F
authors.lastname: Ota
authors.forename: Rie
authors.initials: R
authors.lastname: Nakamura
authors.forename: Koma
authors.initials: K
authors.lastname: Naito
authors.forename: Haruka
authors.initials: H
authors.lastname: Nishiguchi
authors.forename: Sayoko
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamura
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014747:Vinblastine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014747:Vinblastine; D018631:ras Proteins; D002945:Cisplatin; D000077235:Vinorelbine