Podoplanin is associated with metastasis in synovial sarcoma.

2890 Introduction: Synovial sarcomas share features with carcinomas as they can express epithelial markers and metastasize in up to 40% of cases. The present study addresses the role of podoplanin in metastasis of synovial sarcoma. Podoplanin, recognized by the monoclonal antibody D2-40, has been implicated in tumor progression of carcinomas promoting metastasis via an alternative pathway of collective cell invasion, a growth pattern common in sarcomas. As podoplanin expression has frequently been observed in lymphatic vessel networks, the role of lymphangiogenic growth factor VEGF-C is studied, likewise.
 Methods: 30 paraffin-embedded synovial sarcomas were analysed immunohistochemically using the markers D2-40 and VEGF-C. Clinical data including incidence of metastasis and overall survival were available for all cases. In vitro studies focussing on VEGF-C-dependent induction of podoplanin expression and cell migration were performed using 3 different synovial sarcoma cell lines (CME-1, SYO-1, 1273/99).
 Results: Ubiquitous membranous expression of podoplanin was found in 10, focal to absent expression in 20 cases of the paraffin-embedded collective. Podoplanin-overexpressing cases showed collective cell invasion at the tumour invasion front. The incidence of metastasis was significantly higher in this group compared to cases with focal or absent staining reaction (p=0.011). Lymphangiogenic factor VEGF-C was expressed in 23 synovial sarcomas. Strong, often ubiquitous, expression of VEGF-C was seen in the podoplanin-overexpressing subgroup; in contrast, weaker VEGF-C staining was observed in cases with low or absent podoplanin expression (p=0.036). In vitro, 3 synovial sarcoma cell lines showed differential membranous podoplanin expression confirming the findings in paraffin-embedded tissue. Incubation of CME-1 cells with the lymphangiogenic factor VEGF-C induced podoplanin overexpression in western blot and immunofluorescence staining. A higher migratory capacity of the tumor cells was determined in scratch assay after VEGF-C induction.
 Conclusions: Our data indicate an important role of podoplanin in tumor invasion and metastatic spread of synovial sarcomas which is probably mediated by VEGF-C and other growth factors.