Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

Abstract

Canine perivascular wall tumors (PWTs) are a group of subcutaneous soft tissue sarcomas developing from vascular mural cells. Mural cells are involved in angiogenesis through a complex crosstalk with endothelial cells mediated by several growth factors and their receptors. The evaluation of their expression may have relevance since they may represent a therapeutic target in the control of canine PWTs. The expression of vascular endothelial growth factor (VEGF) and receptors VEGFR-I/II, basic fibroblast growth factor (bFGF) and receptor Flg, platelet-derived growth factor B (PDGFB) and receptor PDGFRb, transforming growth factor b1 (TGFb1) and receptors TGFbR-I/II, and cyclooxygenase 2 (COX2) was evaluated on frozen sections of 40 PWTs by immunohistochemistry and semiquantitatively scored to identify their potential role in PWT development. Statistical analysis was performed to analyze possible correlations between Ki67 labeling index and the expression of each molecule. Proteins of the VEGF-, PDGFB-, and bFGF-mediated pathways were highly expressed in 27 (67.5%), 30 (75%), and 19 (47.5%) of 40 PWTs, respectively. Proteins of the TGFb1-and COX2-mediated pathways were highly expressed in 4 (10%) and 14 (35%) of 40 cases. Statistical analysis identified an association between VEGF and VEGFR-I/II (P ¼ .015 and .003, respectively), bFGF and Flg (P ¼ .038), bFGF and PDGFRb (P ¼ .003), and between TGFb1 and COX2 (P ¼ .006). These findings were consistent with the mechanisms that have been reported to play a role in angiogenesis and in tumor development. No association with Ki67 labeling index was found. VEGF-, PDGFB-, and bFGF-mediated pathways seem to have a key role in PWT development and growth. Blockade of tyrosine kinase receptors after surgery could represent a promising therapy with the aim to reduce the PWT relapse rate and prolong the time to relapse.

Reclassification of 21 Presumptive Canine Peripheral Nerve Sheath Tumors (PNST) Using a Literature-Based Immunohistochemical Panel

“…The pathways with the highest expression were those mediated by RTK, including VEGFR, PDGFRβ and FGFR [19]. To the authors' knowledge, this is the fi rst time that EGFR expression is investigated in a cohort of canine STSs.…”

“…The fi rst step in detecting potential differences is to defi ne methods for an accurate classifi cation. Although some recent studies improved the classifi cation of canine PWTs [11,19], there is still considerable overlap of histologic diagnosis between STS types.…”

The controversial histologic classification of canine subcutaneous whorling tumours: The path to perivascular wall tumours

“…40,42 Finally, canine PWTs have been reported to express proteins of vascular endothelial growth factor-, platelet-derived growth factor subunit B-and basic fibroblast growth factor-mediated pathways, suggesting the possible role of these molecules as targets for adjuvant therapy. 45 Nevertheless, studies regarding the efficacy of adjuvant therapies for PWTs, such as the administration of commercially available tyrosine-kinase inhibitors, are lacking, and oncologists should follow the therapy suggested for the generic group of STSs, such as radiation therapy and/or metronomic chemotherapy. 35,43,[45][46][47][48] In summary, the studies published in the last decade have led to a better definition of the origin of 'old' HPC and PWTs clarifying many of the diagnostic features and their peculiar clinical behaviour.…”

“…45 Nevertheless, studies regarding the efficacy of adjuvant therapies for PWTs, such as the administration of commercially available tyrosine-kinase inhibitors, are lacking, and oncologists should follow the therapy suggested for the generic group of STSs, such as radiation therapy and/or metronomic chemotherapy. 35,43,[45][46][47][48] In summary, the studies published in the last decade have led to a better definition of the origin of 'old' HPC and PWTs clarifying many of the diagnostic features and their peculiar clinical behaviour. 13,25,28,33,40,42,45 Several data are still lacking for the complete understanding of canine PWTs, and additional studies are required and should be encouraged to analyse its pathogenesis and therapy.…”

“…In summary, the studies published in the last decade have led to a better definition of the origin of ‘old’ HPC and PWTs clarifying many of the diagnostic features and their peculiar clinical behaviour . Several data are still lacking for the complete understanding of canine PWTs, and additional studies are required and should be encouraged to analyse its pathogenesis and therapy.…”