Immunohistochemical detection of C-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in mantle cell lymphoma.
BACKGROUND
Mantle cell lymphoma (MCL) is a low-grade lymphoproliferative malignancy that is extremely refractory to chemotherapy. Commonly used treatments have yielded unfavorable response rates (30% complete remission). We evaluated the incidence of c-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in patients with MCL in an effort to identify possible targets for therapeutic intervention.


METHODS
Patients with a diagnosis of MCL based on CD5 positivity associated with cyclin D1 positivity and CD23 negativity on the lymph node/bone marrow specimen were included in our retrospective study. CD117 overexpression was performed using immunohistochemistry on archival specimens. VEGF expression was detected by the avidin-biotin-complex method.


RESULTS
Between 1997 and 2001, we identified 17 patients with MCL (9 males, 8 females) with a mean age of 57 years (age range: 42-66 years). The mean overall survival was 34 months (range: 11-60 months). VEGF expression was identified in 7 out of 17 (41.18%) patients with MCL. Among the VEGF-positive patients (n = 7, 41.1%), the mean survival was 24 months (range: 11-42 months), while patients without VEGF expression (n = 10, 58.9%) had a mean survival of 44 months (range: 21-60 months). CD117 expression was identified in only 2 out of 17 (1.17%) patients in our study.


CONCLUSIONS
Our study evaluated the role of c-kit and VEGF overexpression in MCL. Although CD117 may not be of therapeutic significance, target-directed signal transduction inhibition therapy using VEGF-inhibitors may be a distinct possibility in a select group of patients with MCL. Future larger studies are urgently needed to elaborate the role of VEGF in MCL.
Potti
Anil
A
Department of Medicine, University of North Dakota School of Medicine and Health Sciences, Fargo, ND 58102, USA. apotti@medicine.nodak.edu
Ganti
Apar Kishor
AK
Kargas
Steve
S
Koch
Michael
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008222:Lymphokines / Q000096:biosynthesis*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012189:Retrospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019009:Proto-Oncogene Proteins c-kit