Expression of Platelet-Derived Growth Factor Receptor (PDGF-R) and Vascular Endothelial Growth Factor (VEGF) in Intravenous Leiomyomatosis (IVL): An Immunohistochemical Study of 29 Cases
AG McDonald, P Della Pelle, M De Nictolis, E Garcia-Fernandez, D Hardisson, J Prat, E Oliva. Massachusetts General Hospital, Boston, MA; Istituto di Anatomia e Istologia Pathologica, Ancona, Italy; Hospital Universitario La Paz, Madrid, Spain; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Background: PDGF, a powerful mitogen to smooth muscle cells, and VEGF, a critical pro-angiogenic molecule, belong to the family of growth factors and have been shown to have a role in the pathogenesis of a variety of mesenchymal tumors. PDGF, VEGF, and their respective receptors have been implicated in the pathogenesis of leiomyomas but they have not been investigated in IVL of the uterus, an intravascular proliferation of benign smooth muscle cells of unknown etiology.
Design: We evaluated 29 cases of IVL (2 recurrences) in 27 women (mean age 48.2 +/- 10.8 years). Immunohistochemistry for PDGF-R and VEGF was performed in representative tissue sections. Intensity and extent of staining of tumor and myometrium were evaluated by a semiquantitative method as follows: 0 (no staining), 1 (weak), 2 (moderate), and 3 (strong); focal (25%) or diffuse (>25%). Data was analyzed by the Student t-test (bidirectional, p<0.05).
Results: With the exception of one case, the extent of PDGF-R and VEGF staining was diffuse in both IVL and myometrium. However, differences in intensity of staining were seen. Intensity of PDGF-R staining in IVL cases (mean score 2.330.62) was stronger than that of the background myometrium (1.330.44). Similarly, intensity of VEGF staining (mean score 2.360.61) was higher than that seen in the background myometrium (2.120.84). Differences in intensity were statistically significant for both PDGF-R (p<0.001) and VEGF (p=0.04).
Conclusions: Our findings suggest a potential role for PDGF-R and VEGF in the pathogenesis of IVL through proliferation and angiogenesis, perhaps allowing for lymphovascular invasion. Although estrogen and progesterone have been shown to increase expression of PDGF and VEGF leading to the use of anti-hormones in the treatment of IVL, the increased levels of PDGF-R and VEGF suggest that pharmacologic agents targeting tyrosine kinases downstream effectors of PDGF-R and VEGF may be useful in the treatment of these subset of patients.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 166, Wednesday Afternoon