title: Expression of Bcl-2 in gastrointestinal stromal tumors: correlation with progression-free survival in 81 patients treated with imatinib mesylate.
abstract: BACKGROUND
  The natural history of gastrointestinal stromal tumor (GIST) has been revolutionized by imatinib mesylate (imatinib) therapy. Before imatinib, Bcl-2 expression in GIST was associated with a worse prognosis or added no additional prognostic value. To the authors' knowledge, the current study is the first to evaluate Bcl-2 expression in pre-imatinib GIST tissue samples as a prognostic marker of progression-free survival (PFS) time in patients treated with imatinib.
  
  
  METHODS
  The cases of 81 patients with GIST who were evaluated between December 15, 2000 and September 1, 2001 were retrospectively reviewed. Clinicopathologic variables were reviewed. GIST cell morphology and patterns of Bcl-2 expression were described. The methods of Kaplan-Meier and the Cox proportional hazards regression model were used for statistical analysis.
  
  
  RESULTS
  Sixty-one (75%) patients had tumors that expressed Bcl-2, and 20 (25%) patients had tumors that were negative for Bcl-2. All epithelioid tumors (n = 12) expressed Bcl-2 and tumors with mixed morphology exhibited Bcl-2 expression in the epithelioid component. A trend toward longer PFS for patients whose tumors expressed Bcl-2 at a greater immunohistochemical intensity was observed (20.6 mos for no Bcl-2 expression; 28.3 mos for 1++Bcl-2 expression; 31.9 mos for 1.5++Bcl-2 expression; 40.8 mos for 2++Bcl-2 expresssion; and 35.9 mos for 3++Bcl-2 expression).
  
  
  CONCLUSIONS
  In contrast to studies performed in the preimatinib era, in which Bcl-2 was found to be a negative prognostic indicator, the current study suggests a trend toward better PFS with increasing Bcl-2 expression level in GISTs from patients subsequently treated with imatinib. Larger studies may help elucidate the influence of Bcl-2 expression on PFS after therapy with imatinib.
authors.affiliation: Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
authors.forename: Dejka M
authors.initials: DM
authors.lastname: Steinert
authors.forename: Mauricio
authors.initials: M
authors.lastname: Oyarzo
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Haesun
authors.initials: H
authors.lastname: Choi
authors.forename: Peter F
authors.initials: PF
authors.lastname: Thall
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.forename: A Kevin
authors.initials: AK
authors.lastname: Raymond
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Trent
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D000068877:Imatinib Mesylate