Skip to main content

Advertisement

SpringerLink
Log in

Differential expression of angiogenic factors in peripheral nerve sheath tumors

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

It is difficult to differentiate some malignant peripheral nerve sheath tumors (MPNST) from benign peripheral nerve sheath tumors (BPNST) histologically, and to predict the clinical outcome of patients with MPNST. In this study, the expression of VEGF and MVD were evaluated immunohistochemically in 22 cases of MPNST, 14 of neurofibroma and 19 of schwannoma and correlation of the staining grade of VEGF or MVD and the various clinical factors were analyzed, and statistically evaluated. Levels of VEGF mRNA expression were also determined with real-time RT-PCR. Statistically higher positive staining for VEGF was observed in MPNST compared to neurofibroma (P = 0.004) and schwannoma (P < 0.001). Even low grade MPNST showed higher VEGF positive staining than neurofibroma. Moreover, high VEGF expression statistically correlated with the poor prognosis of the patients with MPNST (P = 0.015). Although MVD in MPNST was significantly higher than that in neurofibroma (P = 0.038) and schwannoma (P < 0.001), MVD could not predict the prognosis of the patients with MPNST. Although VEGF mRNA expression tended to be higher in MPNST compared to neurofibroma, the difference was not significant. Levels of VEGF protein expression serve as a novel diagnostic and prognostic tools for peripheral nerve sheath tumors.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

MPNST:

Malignant peripheral nerve sheath tumors

BPNST:

Benign peripheral nerve sheath tumors

VEGF:

Vascular endothelial growth factor

MVD:

Micro vessel density

NF1:

Neurofibromatosis type 1

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

NED:

No evidence of disease

AWD:

Alive with disease

DOD:

Died of disease

References

  1. Enzinger FM, Weiss SW (2001) Malignant tumors of peripheral nerves. In: Enzinger FM, Weiss SW (eds) Soft tissue tumors. CV Mosby Company, St. Louis, pp 1209–1263

    Google Scholar 

  2. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186

    PubMed  CAS  Google Scholar 

  3. Folkman J (1990) What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82(1):4–6

    Article  PubMed  CAS  Google Scholar 

  4. Borre M, Offersen BV, Nerstrom B, Overgaard J (1998) Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting. Br J Cancer 78(7):940–944

    PubMed  CAS  Google Scholar 

  5. Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med 324(1):1–8

    PubMed  CAS  Google Scholar 

  6. Choi JY, Jang KT, Shim YM, Kim K, Ahn G, Lee KH, Choi Y, Choe YS, Kim BT (2006) Prognostic significance of vascular endothelial growth factor expression and microvessel density in esophageal squamous cell carcinoma: comparison with positron emission tomography. Ann Surg Oncol 13:1054–1062

    Article  PubMed  Google Scholar 

  7. Galizia G, Lieto E, Ferraraccio F, Orditura M, De Vita F, Castellano P, Imperatore V, Romano C, Ciardiello F, Agostini B, Pignatelli C (2004) Determination of molecular marker expression can predict clinical outcome in colon carcinomas. Clin Cancer Res 10:3490–3499

    Article  PubMed  CAS  Google Scholar 

  8. Giatromanolaki A, Sivridis E, Brekken R, Thorpe PE, Anastasiadis P, Gatter KC, Harris AL, Koukourakis MI (2001) The angiogenic “vascular endothelial growth factor/flk-1(KDR) receptor” pathway in patients with endometrial carcinoma: prognostic and therapeutic implications. Cancer 92:2569–2577

    Article  PubMed  CAS  Google Scholar 

  9. Imamura M, Yamamoto H, Nakamura N, Oda Y, Yao T, Kakeji Y, Baba H, Maehara Y, Tsuneyoshi M (2007) Prognostic significance of angiogenesis in gastrointestinal stromal tumor. Mod Pathol 20:529–537

    Article  PubMed  CAS  Google Scholar 

  10. Mineo TC, Ambrogi V, Baldi A, Rabitti C, Bollero P, Vincenzi B, Tonini G (2004) Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer. J Clin Pathol 57:591–597

    Article  PubMed  CAS  Google Scholar 

  11. Miracco C, Montesco MC, Santopietro R, Spina D, d’Amore ES, Tosi P, Ninfo V (1996) Proliferative activity, angiogenesis, and necrosis in peripheral nerve sheath tumors: a quantitative evaluation for prognosis. Mod Pathol 9:1108–1117

    PubMed  CAS  Google Scholar 

  12. Arbiser JL, Flynn E, Barnhill RL (1998) Analysis of vascularity of human neurofibromas. J Am Acad Dermatol 38:950–954

    Article  PubMed  CAS  Google Scholar 

  13. Kawachi Y, Xu X, Ichikawa E, Imakado S, Otsuka F (2003) Expression of angiogenic factors in neurofibromas. Exp Dermatol 12(4):412–417

    Article  PubMed  CAS  Google Scholar 

  14. Lin BT, Weiss LM, Medeiros LJ (1997) Neurofibroma and cellular neurofibroma with atypia: a report of 14 tumors. Am J Surg Pathol 21:1443–1449

    Article  PubMed  CAS  Google Scholar 

  15. DuBois S, Demetri G (2007) Markers of angiogenesis and clinical features in patients with sarcoma. Cancer 109(5):813–819

    Article  PubMed  CAS  Google Scholar 

  16. Saenz NC, Heslin MJ, Adsay V, Lewis JJ, Leung DH, LaQuaglia MP, Brennan MF (1998) Neovascularity and clinical outcome in high-grade extremity soft tissue sarcomas. Ann Surg Oncol 5:48–53

    Article  PubMed  CAS  Google Scholar 

  17. Yudoh K, Kanamori M, Ohmori K, Yasuda T, Aoki M, Kimura T (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

    Article  PubMed  CAS  Google Scholar 

  18. Chao C, Al-Saleem T, Brooks JJ, Rogatko A, Kraybill WG, Eisenberg B (2001) Vascular endothelial growth factor and soft tissue sarcomas: tumor expression correlates with grade. Ann Surg Oncol 8:260–267

    Article  PubMed  CAS  Google Scholar 

  19. Pakos EE, Goussia AC, Tsekeris PG, Papachristou DJ, Stefanou D, Agnantis NJ (2005) Expression of vascular endothelial growth factor and its receptor, KDR/Flk-1, in soft tissue sarcomas. Anticancer Res 25:3591–3596

    PubMed  CAS  Google Scholar 

  20. Kaya M, Wada T, Akatsuka T, Kawaguchi S, Nagoya S, Shindoh M, Higashino F, Mezawa F, Okada F, Ishii S (2000) Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Clin Cancer Res 6:572–577

    PubMed  CAS  Google Scholar 

  21. Kreuter M, Paulussen M, Boeckeler J, Gerss J, Buerger H, Liebscher C, Kessler T, Jurgens H, Berdel WE, Mesters RM (2006) Clinical significance of vascular endothelial growth factor-A expression in Ewing’s sarcoma. Eur J Cancer 42(12):1904–1911

    Article  PubMed  CAS  Google Scholar 

  22. Kreuter M, Bieker R, Bielack SS, Auras T, Buerger H, Gosheger G, Jurgens H, Berdel WE, Mesters RM (2004) Prognostic relevance of increased angiogenesis in osteosarcoma. Clin Cancer Res 10:8531–8537

    Article  PubMed  Google Scholar 

  23. Charity RM, Foukas AF, Deshmukh NS, Grimer RJ (2006) Vascular endothelial growth factor expression in osteosarcoma. Clin Orthop Relat Res 448:193–198

    Article  PubMed  CAS  Google Scholar 

  24. Mantadakis E, Kim G, Reisch J, McHard K, Maale G, Leavey PJ, Timmons C (2001) Lack of prognostic significance of intratumoral angiogenesis in nonmetastatic osteosarcoma. J Pediatr Hematol Oncol 23:286–289

    Article  PubMed  CAS  Google Scholar 

  25. Wang D, Chen L, Gao F (1997) [Correlation of tumor microvesseldensity with prognosis in osteogenic sarcoma]. Zhonghua Bing Li Xue Za Zhi 26:266–269

    Google Scholar 

  26. Anghileri M, Miceli R, Fiore M, Mariani L, Ferrari A, Mussi C, Lozza L, Collini P, Olmi P, Casali PG, Pilotti S, Gronchi A (2006) Malignant peripheral nerve sheath tumors: prognostic factors and survival in a series of patients treated at a single institution. Cancer 107(5):1065–1074

    Article  PubMed  Google Scholar 

  27. Baehring JM, Betensky RA, Batchelor TT (2003) Malignant peripheral nerve sheath tumor: the clinical spectrum and outcome of treatment. Neurology 61(5):696–698

    PubMed  Google Scholar 

  28. Cashen DV, Parisien RC, Raskin K, Hornicek FJ, Gebhardt MC, Mankin HJ (2004) Survival data for patients with malignant schwannoma. Clin Orthop Relat Res 426:69–73

    Article  PubMed  Google Scholar 

  29. Kar M, Deo SS, Shukla NK, Malik A, Dattagupta S, Mohanti BK, Thulkar S (2006) Malignant peripheral nerve sheath tumors (MPNST)—clinicopathological study and treatment outcome of twenty-four cases. World J Surg Oncol 4:55

    Article  PubMed  Google Scholar 

  30. Okada K, Hasegawa T, Tajino T, Hotta T, Yanagisawa M, Osanai T, Nishida J, Seki K, Itoi E (2007) Clinical relevance of pathological grades of malignant peripheral nerve sheath tumor: a multi-institution TMTS study of 56 cases in Northern Japan. Ann Surg Oncol 14(2):597–604

    Article  PubMed  Google Scholar 

  31. Wanebo JE, Malik JM, VandenBerg SR, Wanebo HJ, Driesen N, Persing JA (1993) Malignant peripheral nerve sheath tumors. A clinicopathologic study of 28 cases. Cancer 71(4):1247–1253

    Article  PubMed  CAS  Google Scholar 

  32. Wong WW, Hirose T, Scheithauer BW, Schild SE, Gunderson LL (1998) Malignant peripheral nerve sheath tumor: analysis of treatment outcome. Int J Radiat Oncol Biol Phys 42(2):351–360

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Mr. Hiroshi Yamada for technical assistance to make tissue sections, and Miss Eri Ishihara for secretarial assistance. This work was supported in part by The Nakatomi Foundation, and by the Ministry of Education, Culture, Sports, Science and Technology of Japan [Grant-in-Aid 20591751 for Scientific Research (C)].

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65-Tsuruma, Showa, Nagoya, 466-8550, Japan

    Junji Wasa, Yoshihiro Nishida, Yoshitaka Suzuki, Satoshi Tsukushi, Yoji Shido, Kozo Hosono & Naoki Ishiguro

  2. Department of Pathology and Clinical Laboratories, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshie Shimoyama & Shigeo Nakamura

Authors
  1. Junji Wasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshihiro Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshitaka Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoshi Tsukushi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoji Shido
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kozo Hosono
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshie Shimoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shigeo Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Naoki Ishiguro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshihiro Nishida.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wasa, J., Nishida, Y., Suzuki, Y. et al. Differential expression of angiogenic factors in peripheral nerve sheath tumors. Clin Exp Metastasis 25, 819–825 (2008). https://doi.org/10.1007/s10585-008-9197-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-008-9197-8

Keywords

Search

Navigation