Immunohistochemical detection of HER-2/neu, c-kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas.
OBJECTIVE
The aim of this study was to determine the incidence of HER-2/neu, VEGF and CD117 overexpression in soft tissue sarcomas (STS) and to study the effect of this overexpression, if present, on survival in patients with specific histological subtypes of STS.


METHODS
We conducted a retrospective observational study on patients diagnosed with STS during the period of 1986-2001. HER-2/neu overexpression was measured in these patients by immunohistochemistry (IHC) using the Hercep test developed by DAKO. VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). Immunohistochemical staining for c-kit was performed using a 1:250 dilution of the rabbit polyclonal antibody A4502 (IMPATH, CA) with the EnVision detection system.


RESULTS
Two hundred and seventy three patients were diagnosed as having STS between 1986 and 2001, however of these patients, only 90 (51 females and 49 males) had enough sample available for testing. Patients who overexpressed VEGF had a significantly shorter survival (23 vs. 52 months; p=0.01). There was no effect of overexpression of either CD117 or HER-2/neu on survival. Studying the individual histological subtypes we found that, in malignant fibrous histiocytoma, overexpression of either VEGF or CD117 increased survival (41.3 vs. 19.5 months, p=0.01; and 84.5 vs. 17 months, p=0.006 respectively). In leiomyosarcoma, VEGF overexpression significantly decreased survival (7.5 vs. 76 months, p=0.03), while CD117 overexpression significantly increased survival (70.9 vs. 46.3 months, p=0.03).


CONCLUSIONS
VEGF overexpression is associated with an adverse outcome in STS. Whether this is true of any particular histological subtype is unclear and needs further investigation. Also, site-specific agents targeting these three bio-markers (alone or with conventional therapy) may have a therapeutic role and need to be elaborated in future clinical trials.
Potti
Anil
A
Department of Medicine, University of North Dakota School of Medicine, Fargo, ND 58102, USA.
Ganti
Apar Kishor
AK
Foster
Heidi
H
Knox
Stacey
S
Hebert
Brian J
BJ
Tendulkar
Ketki
K
Sholes
Kaley
K
Koch
Michael
M
Kargas
Steven
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012189:Retrospective Studies; D012509:Sarcoma / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000378:metabolism*; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A