title: Coexpression of fragile histidine triad and c-kit is relevant for prediction of survival in patients with small cell lung cancer.
abstract: BACKGROUND
  In a retrospective analysis of 195 patients with small cell lung cancer (SCLC), we examined the prognostic value of a coexpression of fragile histidine triad (FHIT) protein and c-kit on patient's survival.
  
  
  METHODS
  As assessed by immunohistochemistry using formalin-fixed, paraffin-embedded tissue sections, tumors of 195 patients with SCLC were evaluated for FHIT and c-kit coexpression.
  
  
  RESULTS
  Coexpression of FHIT and c-kit was observed in 53.3%; a positive expression of either FHIT or c-kit was found in 40.5%. Complete lack of FHIT and c-kit (6.2%) was associated with a significantly shorter survival time for the patients with a mean of 122 +/- 45 days compared with 468 +/- 89 days for patients with lung cancer coexpressing FHIT and c-kit (P = 0.0011). The proportion of FHIT- and c-kit-positive cells within a tumor was also related to survival time. Patients with tumors with a proportion between 0% to 25% of FHIT- and c-kit-positive cells had the worst survival of 157 +/- 34 days compared with 496 +/- 95 days for patients showing >25% FHIT- and c-kit-positive cells (P = 0.0002). Further, variables associated with shorter survival times were low performance status, elevated lactate dehydrogenase level, and advanced tumor stage according to tumor-node-metastasis classification. Multivariate analysis using Cox regression model, including 11 variables, confirmed the prognostic significance of a combined expression of FHIT and c-kit next to tumor stage, performance status, and lactate dehydrogenase level.
  
  
  CONCLUSIONS
  Differential FHIT and c-kit expression was of prognostic relevance for survival in patients with SCLC and therefore provide useful variables for therapeutic decisions.
authors.affiliation: Klinik für Hämatologie, Onkologie und klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Dusseldorf, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Rehfeld
authors.forename: Helene
authors.initials: H
authors.lastname: Geddert
authors.forename: Abedelsalam
authors.initials: A
authors.lastname: Atamna
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Gabbert
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steidl
authors.forename: Roland
authors.initials: R
authors.lastname: Fenk
authors.forename: Ralf
authors.initials: R
authors.lastname: Kronenwett
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Ulrich-Peter
authors.initials: UP
authors.lastname: Rohr
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000401:mortality*; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D007770:L-Lactate Dehydrogenase; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D000099170:Bis(5'-adenosyl)triphosphatase