Metastatic Solitary Fibrous Tumor/Hemangiopericytoma Overexpresses Multiple Growth Factors
Elizabeth G Demicco, Dejka Araujo, Jon Trent, Alexander J Lazar, Wei-Lien Wang. The University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Solitary fibrous tumor (SFT)/ Hemangiopericytoma (HPC) is a mesenchymal tumor of uncertain origin with notoriously unpredictable behavior. Little is known about the signaling pathways underlying tumor progression and metastasis. We studied expression of growth hormones and receptors and their potential prognostic significance in a large series of metastatic and primary SFT/HPC. Comparison with meningeal (CNS) tumors, which are reported to behave more aggressively than in other sites, was also made.
Design: Tissue microarray (TMA) was constructed from 114 tumors from 95 patients, and included 88 soft tissue (ST) SFT/HPCs and 26 CNS HPCs. There were 67 primaries, 39 metastases, and 8 recurrent tumors. Clinical follow-up was available for 55 soft tissue primaries. Immunohistochemistry (IHC) included: IGF1R, EGFR PDGFR-α, PDGFR-β, PDGF-α, PDGF-β, VEGF, cerbB2, ER, and PR. IHC was scored by extent and degree and compared using χ2 or Fisher exact test.
Results: Compared to primary tumors, metastatic ST tumors had higher expression of growth factors (VEGF, 39% vs. 11%, p<0.01; PDGF-β 67% vs. 27% p<0.001; PDGF-α, 25% vs. 9%, p=0.08) and growth factor receptors PDGFR-α and -β (69% vs. 33%, p=0.002; 63% vs. 38% p=0.046). Metastases from CNS tumors trended toward elevated levels of PDGFR-α and VEGF only (56% vs. 10%, p=.057; 67% vs. 20%, p=0.07, respectively). ST primaries trended toward lower expression of both PDGF-α and β, compared to CNS primaries (9% vs. 30%, p=0.098, and 27% vs.60%, p=0.065). Moderate to high PR was seen in 38% of ST primaries and no CNS primaries (p=0.024). No significant difference was seen in IGF1R, EGFR or ER between primary and metastatic disease. All tumors were negative for cerbB2. No significant differences in expression were seen between 9 primary ST tumors which metastasized and 45 that did not.
Conclusions: While growth factor expression was not prognostic in primary tumors, increased expression of multiple growth factors and receptors was seen in metastatic HPC/SFT, suggesting a role in tumor progression. Moreover, CNS primary tumors express more PDGF-α and β than ST tumors, and this may play a role in the more aggressive behavior of these tumors. Targeted therapy against growth factor signaling pathways warrants additional consideration in SFT/HPC. Correlation with histological parameters is on-going.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 33, Monday Afternoon