Abstract
Purpose
To evaluate the prevalence and role of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcoma (STS).
Patients and methods
VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). The expression of VEGF was assessed according to the percentage of immunoreactive cells: more than 10% of the cells staining were graded as positive. No detectable staining or <10% (of cells) staining was graded as negative.
Results
Two hundred and seventy-three patients (164 females and 109 males) with a mean age of 56 years (range: 1–93 years) were included in the study. Sixty-eight of the 273 (24.91%) patients diagnosed with STS between 1986 and 2001 revealed VEGF overexpression. VEGF overexpression was predominantly seen in 30% (15/50) of patients with malignant fibrous histiocytoma (MFH), 20.45% (9/44) of dermatofibrosarcomas (DFS), 25% (9/36) of leiomyosarcomas (LMS), and 30% (6/20) of patients with carcinosarcomas (CS). Despite overexpression being seen in about a quarter of patients with STS, VEGF overexpression was of prognostic value in only those patients with the LMS histologic type, as VEGF overexpression was associated with a shorter survival in this subgroup(P=0.01, by log-rank sum test).
Conclusion
Twenty-four point nine per centof STS overexpress VEGF and interestingly there is diversity seen in VEGF expression amongst the various histologic subtypes of STS. LMS, CS, and MFH are more likely to reveal overexpression of VEGF than the other histologic subtypes. There was no relationship between survival and VEGF status in any subtype of STS, except LMS. There is an urgent need for larger studies to validate our findings. In addition, randomized clinical trials evaluating the efficacy of angiogenesis inhibitors in soft tissue sarcomas, especially LMS, are warranted.
Similar content being viewed by others
References
Antman KH (1997) Adjuvant therapy of sarcomas of soft tissue. Semin Oncol 24:556–560
Brekken RA, Huang X, King SW, Thorpe PE (1998) Vascular endothelial growth factor as a marker of tumor endothelium. Cancer Res 58:1952–1959
Brekken RA, Overholser JP, Stastny VA, et al (2000) Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. Cancer Res 60:5117–5124
Brown LF, Berse B, Jackman RW, et al (1993) Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 143:1255–1262
Chao C, Al-Saleem T, Brooks JJ, et al (2001) Vascular endothelial growth factor and soft tissue sarcomas: tumor expression correlates with grade. Ann Surg Oncol 8:260–267
Emoto M, Iwasaki H, Ishiguro M, et al (1999) Angiogenesis in carcinosarcomas of the uterus: differences in the microvessel density and expression of vascular endothelial growth factor between the epithelial and mesenchymal elements. Hum Pathol 30:1232–1241
Ferrara N, Henzel WJ (1989) Pituitary follicular cells secrete a novel heparin- binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851–859
Goldman CK, Kendall RL, Cabrera G, et al (1998) Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate. Proc Natl Acad Sci USA 95:8795–8800
Guidi AJ, Abu-Jawdeh G, Berse B, et al (1995) Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J Natl Cancer Inst 87:1237–1245
Hasan J, Jayson GC (2001) VEGF antagonists. Expert Opin Biol Ther 1:703–718
Hong T, Shimada Y, Uchida S, et al (2001) Expression of angiogenic factors and apoptotic factors in leiomyosarcoma and leiomyoma. Int J Mol Med 8:141–148
Iyoda A, Hiroshima K, Baba M, et al (2001) Expression of vascular endothelial growth factor in thoracic sarcomas. Ann Thorac Surg 71:1635–1639
Jemal A, Thomas A, Murray T, Thun M (2002) Cancer statistics, 2002. CA Cancer J Clin 52:23–47
Kawauchi S, Fukuda T, Tsuneyoshi M (1999) Angiogenesis does not correlate with prognosis or expression of vascular endothelial growth factor in synovial sarcomas. Oncol Rep 6:959–964
Kaya M, Wada T, Akatsuka T, et al (2000) Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res 6:572–577
Kerbel RS (1997) A cancer therapy resistant to resistance. Nature 390:335–336
Kong HL, Hecht D, Song W, et al (1998) Regional suppression of tumor growth by in vivo transfer of a cDNA encoding a secreted form of the extracellular domain of the flt-1 vascular endothelial growth factor receptor. Human Gene Ther 9:823–833
Kuhnen C, Lehnhardt M, Tolnay E, et al (2000) Patterns of expression and secretion of vascular endothelial growth factor in malignant soft-tissue tumours. J Cancer Res Clin Oncol 126:219–225
Maeda K, Chung YS, Ogawa Y, et al (1996) Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer 77:858–863
Mattern J, Koogami R, Volm M (1995) Vascular endothelial growth factor expression and angiogenesis in non-small cell lung carcinomas. Int J Oncol 6:1059–1062
Mise M, Arii S, Higashituju H, et al (1996) Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor. Hepatology 23:455–464
Olson TA, Mohanraj D, Ramakrishnan S (1995) The selective inhibition of vascular permeability factor (VPF) expression in ovarian carcinoma cell lines by gonadotropin releasing hormone (GnRH) agonist. Int J Oncol 6:905–910
Presta LG, Chen H, O’Connor SJ, et al (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593–4599
Sato K, Terada K, Sugiyama T, et al (1994) Frequent overexpression of vascular endothelial growth factor gene in human renal cell carcinoma. Tohoku J Exp Med 173:355–360
Senger DR, Galli SJ, Dvorack AM, et al (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (Wash DC) 219:983–985
Takahashi Y, Tucker SL, Kitada Y, et al (1997) Vessel count and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer. Arch Surg 32:541–546
Toi M, Hoshina T, Takayanagi T, Tomianga T (1994) Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn J Cancer Res 85:1045–1049
Yudoh K, Kanamori M, Ohmori K, et al (2001) Concentration of vascular endothelial growth factor in the tumour tissue as a prognostic factor of soft tissue sarcomas. Br J Cancer 84:1610–1615
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Potti, A., Ganti, A.K., Tendulkar, K. et al. Determination of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcomas and the role of overexpression in leiomyosarcoma. J Cancer Res Clin Oncol 130, 52–56 (2004). https://doi.org/10.1007/s00432-003-0504-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-003-0504-0