Skip to main content

Advertisement

Log in

Contrasting Prognostic Implications of Platelet-Derived Growth Factor Receptor-β and Vascular Endothelial Growth Factor Receptor-2 in Patients with Angiosarcoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Angiosarcoma is an extremely rare tumor among sarcomas and comprises a heterogeneous group of high-grade vascular malignancies. Our study aimed to examine the correlations between 6 immunohistochemical biomarkers—stem cell factor receptor (KIT), platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and VEGFR-3—and overall survival (OS) in patients with angiosarcomas.

Methods

Immunohistochemical analyses for the 6 biomarkers were performed by using tumor specimens obtained from 34 patients with angiosarcomas. Correlations between biomarkers were examined by Fisher’s exact test. For each biomarker, the correlation between the immunohistochemical score and OS was examined by the log-rank test and Cox regression analysis.

Results

The percentages of angiosarcoma patients with positive expressions (immunohistochemical score > 0) of KIT, PDGFR-α, PDGFR-β, VEGFR-1, VEGFR-2, and VEGFR-3 were 14.7%, 11.8%, 88.2%, 61.8%, 94.1%, and 100.0%, respectively. No statistically significant correlations between any 2 biomarkers were observed. Cox regression analysis demonstrated a significant positive correlation between short OS and the immunohistochemical score for PDGFR-β and between long OS and the immunohistochemical score for VEGFR-2.

Conclusion

Increased expression of PDGFR-β may be a statistically significant prognostic factor for poor OS, while increased expression of VEGFR-2 may be a favorable prognostic factor for patients with angiosarcoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Naka N, Ohsawa M, Tomita Y, et al. Prognostic factors in angiosarcoma: multivariate analysis of 55 cases. J Surg Oncol. 1996;61:170–6.

    Article  PubMed  CAS  Google Scholar 

  2. Otis CN, Peschel R, McKhann C, Merino MJ, Duray PH. The rapid onset of cutaneous angiosarcoma after radiotherapy for breast carcinoma. Cancer. 1986;57:2130–4.

    Article  PubMed  CAS  Google Scholar 

  3. Benda JA, Al-Jurf AS, Benson AB III. Angiosarcoma of the breast following segmental mastectomy complicated by lymphedema. Am J Clin Pathol. 1987;87:651–5.

    PubMed  CAS  Google Scholar 

  4. Fayette J, Martin E, Piperno-Neumann S, et al. Angiosarcomas, a heterogeneous group of sarcomas with specific behavior depending on primary site: a retrospective study of 161 cases. Ann Oncol. 2007;18:2030–6.

    Article  PubMed  CAS  Google Scholar 

  5. Lahat G, Dhuka AR, Hallevi H, et al. Angiosarcoma: clinical and molecular insights. Ann Surg. 2010;251:1098–106.

    Article  PubMed  Google Scholar 

  6. Verweij J, Baker LH. Future treatment of soft tissue sarcomas will be driven by histological subtype and molecular aberrations. Eur J Cancer. 2010;46:863–8.

    Article  PubMed  CAS  Google Scholar 

  7. Ordóñez JL, Martins AS, Osuna D, Madoz-Gurpide J, de Alava E. Targeting sarcomas: therapeutic targets and their rational. Semin Diagn Pathol. 2008;25:304–16.

    Article  PubMed  Google Scholar 

  8. Behrens C, Lin HY, Lee JJ, et al. Immunohistochemical expression of basic fibroblast growth factor and fibroblast growth factor receptors 1 and 2 in the pathogenesis of lung cancer. Clin Can Res. 2008;14:6014–22.

    Article  CAS  Google Scholar 

  9. Shet T, Malaviya A, Nadkarni M, et al. Primary angiosarcoma of the breast: observations in Asian Indian women. J Surg Oncol. 2006;94:368–74.

    Article  PubMed  Google Scholar 

  10. Hornick JL, Fletcher CD. Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution. Am J Clin Pathol. 2002;117:188–93.

    Article  PubMed  Google Scholar 

  11. Komdeur R, Hoekstra HJ, Molenaar WM, et al. Clinicopathologic assessment of postradiation sarcomas: KIT as a potential treatment target. Clin Cancer Res. 2003;9:2926–32.

    PubMed  CAS  Google Scholar 

  12. Miettinen M, Sarlomo-Rikala M, Lasota J. KIT expression in angiosarcomas and fetal endothelial cells: lack of mutations of exon 11 and exon 17 of C-kit. Mod Pathol. 2000;13:536–41.

    Article  PubMed  CAS  Google Scholar 

  13. Palman C, Bowen-Pope DF, Brooks JJ. Platelet-derived growth factor receptor (beta-subunit) immunoreactivity in soft tissue tumors. Lab Invest. 1992;66:108–15.

    PubMed  CAS  Google Scholar 

  14. Itakura E, Yamamoto, H, Oda Y, et al. Detection and characterization of vascular endothelial growth factors and their receptors in a series of angiosarcomas. J Surg Oncol. 2008;97:74–81.

    Article  PubMed  Google Scholar 

  15. Tokuyama W, Mikami T, Masuzawa M, Okayasu I. Autocrine and paracrine roles of VEGF/VEGFR-2 and VEGF-C/VEGFR-3 signaling in angiosarcomas of the scalp and face. Hum Pathol. 2010;41:407–14.

    Article  PubMed  CAS  Google Scholar 

  16. Stacher E, Gruber-Mösenbacher U, Halbwedl I, et al. The VEGF-system in primary pulmonary angiosarcomas and haemangioendotheliomas: new potential therapeutic targets? Lung Cancer. 2009;65:49–55.

    Article  PubMed  Google Scholar 

  17. Hashimoto M, Ohsawa M, Ohnishi A, et al. Expression of vascular endothelial growth factor and its receptor mRNA in angiosarcoma. Lab Invest. 1995;73:859–63.

    PubMed  CAS  Google Scholar 

  18. Partanen TA, Alitalo K, Miettinen M. Lack of lymphatic vascular specificity of vascular endothelial growth factor receptor 3 in 185 vascular tumors. Cancer. 1999;86:2606–12.

    Article  Google Scholar 

  19. Folpe AL, Veikkola T, Valtola R, Weiss SW. Vascular endothelial growth factor receptor-3 (VEGFR-3): a marker of vascular tumors with presumed lymphatic differentiation, including Kaposi’s sarcoma, kaposiform and Dabska-type hemangioendotheliomas, and a subset of angiosarcomas. Mod Pathol. 2000;13:180–5.

    Article  PubMed  CAS  Google Scholar 

  20. Ghosh S, Sullivan CA, Zerkowski MP, et al. High levels of vascular endothelial growth factor and its receptors (VEGFR-1, VEGFR-2, neuropilin-1) are associated with worse outcome in breast cancer. Hum Pathol. 2008;39:1835–43.

    Article  PubMed  CAS  Google Scholar 

  21. Okita NT, Yamada Y, Takahari D, et al. Vascular endothelial growth factor receptor expression as a prognostic marker for survival in colorectal cancer. Jpn J Clin Oncol. 2009;39:595–600.

    Article  PubMed  Google Scholar 

  22. Carrillo de Santa Pau E, Arias FC, Caso Peláez E et al (2009) Prognostic significance of the expression of vascular endothelial growth factors A, B, C, and D and their receptors R1, R2, and R3 in patients with nonsmall cell lung cancer. Cancer. 115:1701–12.

    Article  PubMed  Google Scholar 

  23. Amo Y, Masuzawa M, Hamada Y, Katsuoka K. Serum concentrations of vascular endothelial growth factor-D in angiosarcoma patients. Br J Dermatol. 2004;150:160–1.

    Article  PubMed  CAS  Google Scholar 

  24. Kubo T, Piperdi S, Rosenblum J, Antonescu CR, et al. Platelet-derived growth factor receptor as a prognostic marker and a therapeutic target for imatinib mesylate therapy in osteosarcoma. Cancer. 2008;112:2119–29.

    Article  PubMed  CAS  Google Scholar 

  25. Uren A, Merchant MS, Sun CJ, et al. Beta-platelet-derived growth factor receptor mediates motility and growth of Ewing’s sarcoma cells. Oncogene. 2003;22:2334–42.

    Article  PubMed  CAS  Google Scholar 

  26. Sulzbacher I, Birner P, Trieb K, Muhlbauer M, Lang S, Chott A. Platelet-derived growth factor-alpha receptor expression supports the growth of conventional chondrosarcoma and is associated with adverse outcome. Am J Surg Pathol. 2001;25:1520–7.

    Article  PubMed  CAS  Google Scholar 

  27. Penel N, Bui BN, Bay JO, Cupissol D, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol. 2008;26:5269–74.

    Article  PubMed  CAS  Google Scholar 

  28. Belotti D, Vergani V, Drudis T, et al. The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin Cancer Res. 1996;2:1843–49.

    PubMed  CAS  Google Scholar 

  29. Maki RG, D’Adamo DR, Keohan ML, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol. 2009;27:3133–40.

    Article  PubMed  CAS  Google Scholar 

  30. Kumar R, Crouthamel MC, Rominger DH, et al. Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors. Br J Cancer. 2009;101:1717–23.

    Article  PubMed  CAS  Google Scholar 

  31. Antonescu CR, Yoshida A, Guo T, et al. KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors. Cancer Res. 2009;69:7175–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported by a science research grant (21-tokushi-1) from the Ministry of Health, Labor, and Welfare of Japan. The Ministry had no involvement in the study design; the collection, analysis, or interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication. We thank Dr. Kenjiro Namikawa (Department of Dermatology, National Cancer Center Hospital), Dr. Akira Kawai and Dr. Yasuo Beppu (Department of Orthopedic Surgery, National Cancer Center Hospital), Taizo Hirata, Chikako Shimizu, Noriyuki Katsumata, and Kenji Tamura (Breast and Medical Oncology Division) for treating the patients.

Conflict of interest

Yasuhiro Fujiwara received research funding from Pfizer, GlaxoSmithKline, Chugai-Pharmaceutical, Eisai, Daiichi Sankyo, Taiho Pharmaceutical, and Nihon Kayaku. The other authors declare no conflict of interest

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kan Yonemori MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yonemori, K., Tsuta, K., Ando, M. et al. Contrasting Prognostic Implications of Platelet-Derived Growth Factor Receptor-β and Vascular Endothelial Growth Factor Receptor-2 in Patients with Angiosarcoma. Ann Surg Oncol 18, 2841–2850 (2011). https://doi.org/10.1245/s10434-011-1640-4

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-011-1640-4

Keywords

Navigation