Expression of Bcl-2 in gastrointestinal stromal tumors: correlation with progression-free survival in 81 patients treated with imatinib mesylate.
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.
Steinert
Dejka M
DM
Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
Oyarzo
Mauricio
M
Wang
Xuemei
X
Choi
Haesun
H
Thall
Peter F
PF
Medeiros
L Jeffrey
LJ
Raymond
A Kevin
AK
Benjamin
Robert S
RS
Zhang
Wei
W
Trent
Jonathan C
JC
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
D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D000068877:Imatinib Mesylate