Platelet-Derived Growth Factors in Non-GIST Soft-Tissue Sarcomas Identify a Subgroup of Patients with Wide Resection Margins and Poor Disease-Specific Survival

Overview

Journal Sarcoma

Publisher Wiley

Date 2011 Feb 19

PMID 21331156

Citations 6

Authors

Thomas Karsten Kilvaer

Andrej Valkov

Sveinung W Sorbye

Tom Donnem

Eivind Smeland

Roy Martin Bremnes

Lill-Tove Busund

Affiliations

Soon will be listed here.

Abstract

Background. Optimal treatment of nongastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) is resection with wide margins. This study investigates the prognostic impact of the angiogenesis-associated platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in non-GIST STS patients with wide and nonwide resection margins. Method. Tumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expression of PDGF-A, -B, -C, and -D and PDGFR-α and -β. Results. In the multivariate analysis of patients with wide resection margins, high expression of PDGF-B (P = .013, HR = 2.954, and 95% CI = 1.255-6.956) and the coexpression of PDGF-B and PDGFR-α (overall; P = .016, high-low/low-high; P = .051, HR = 2.678, 95% CI = 0.996-7.200, high/high; P = .004, HR = 3.930, 95% CI = 1.542-10.015) were independent negative prognostic markers for disease-specific survival. Conclusion. PDGF-B and the coexpression of PDGF-B and PDGFR-α are strong and independent prognostic factors in non-GIST STSs with wide resection margins.

Citing Articles

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References

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M . Cancer statistics, 2009. CA Cancer J Clin. 2009; 59(4):225-49. DOI: 10.3322/caac.20006. View

McArthur G . Dermatofibrosarcoma protuberans: recent clinical progress. Ann Surg Oncol. 2007; 14(10):2876-86. DOI: 10.1245/s10434-007-9480-y. View

Pietras K, Stumm M, Hubert M, Buchdunger E, Rubin K, Heldin C . STI571 enhances the therapeutic index of epothilone B by a tumor-selective increase of drug uptake. Clin Cancer Res. 2003; 9(10 Pt 1):3779-87. View

Ostman A . PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev. 2004; 15(4):275-86. DOI: 10.1016/j.cytogfr.2004.03.002. View

Abramsson A, Lindblom P, Betsholtz C . Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. J Clin Invest. 2003; 112(8):1142-51. PMC: 213487. DOI: 10.1172/JCI18549. View

Pietras K, Rubin K, Sjoblom T, Buchdunger E, Sjoquist M, Heldin C . Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res. 2002; 62(19):5476-84. View

Koon H, Bubley G, Pantanowitz L, Masiello D, Smith B, Crosby K . Imatinib-induced regression of AIDS-related Kaposi's sarcoma. J Clin Oncol. 2004; 23(5):982-9. DOI: 10.1200/JCO.2005.06.079. View

Wardelmann E, Schildhaus H, Merkelbach-Bruse S, Hartmann W, Reichardt P, Hohenberger P . Soft tissue sarcoma: from molecular diagnosis to selection of treatment. Pathological diagnosis of soft tissue sarcoma amid molecular biology and targeted therapies. Ann Oncol. 2010; 21 Suppl 7:vii265-9. DOI: 10.1093/annonc/mdq381. View

Thornton K . Chemotherapeutic management of soft tissue sarcoma. Surg Clin North Am. 2008; 88(3):647-60, viii. DOI: 10.1016/j.suc.2008.03.004. View

10.

Tallquist M, Kazlauskas A . PDGF signaling in cells and mice. Cytokine Growth Factor Rev. 2004; 15(4):205-13. DOI: 10.1016/j.cytogfr.2004.03.003. View

11.

Lindblom P, Gerhardt H, Liebner S, Abramsson A, Enge M, Hellstrom M . Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev. 2003; 17(15):1835-40. PMC: 196228. DOI: 10.1101/gad.266803. View

12.

Betsholtz C . Insight into the physiological functions of PDGF through genetic studies in mice. Cytokine Growth Factor Rev. 2004; 15(4):215-28. DOI: 10.1016/j.cytogfr.2004.03.005. View

13.

Hueman M, Schulick R . Management of gastrointestinal stromal tumors. Surg Clin North Am. 2008; 88(3):599-614, vii. DOI: 10.1016/j.suc.2008.03.001. View

14.

Baselga J . Targeting tyrosine kinases in cancer: the second wave. Science. 2006; 312(5777):1175-8. DOI: 10.1126/science.1125951. View

15.

Heldin C, Rubin K, Pietras K, Ostman A . High interstitial fluid pressure - an obstacle in cancer therapy. Nat Rev Cancer. 2004; 4(10):806-13. DOI: 10.1038/nrc1456. View

16.

Sleijfer S, van der Graaf W, Blay J . Angiogenesis inhibition in non-GIST soft tissue sarcomas. Oncologist. 2008; 13(11):1193-200. DOI: 10.1634/theoncologist.2008-0188. View

17.

Kaushal A, Citrin D . The role of radiation therapy in the management of sarcomas. Surg Clin North Am. 2008; 88(3):629-46, viii. PMC: 2517216. DOI: 10.1016/j.suc.2008.03.005. View

18.

Lewis J, Leung D, Woodruff J, Brennan M . Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution. Ann Surg. 1998; 228(3):355-65. PMC: 1191491. DOI: 10.1097/00000658-199809000-00008. View

19.

Wang J, Coltrera M, Gown A . Cell proliferation in human soft tissue tumors correlates with platelet-derived growth factor B chain expression: an immunohistochemical and in situ hybridization study. Cancer Res. 1994; 54(2):560-4. View

20.

Shimizu A, OBrien K, Sjoblom T, Pietras K, Buchdunger E, Collins V . The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res. 1999; 59(15):3719-23. View