Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours

AIMS: Fibroblast activation protein (FAP)/seprase and dipeptidylpeptidase-IV (DPP-IV)/CD26 are serine integral membrane proteases. They are involved in tissue remodelling, cancer invasion and metastases, mechanisms that are controversial. The aim was to identify cell types that express FAP and DPP-IV in human bone and soft tissue tumours, and to determine whether there are any correlations between the expression of FAP and DPP-IV and the malignant potential of tumours. METHODS AND RESULTS: This study analysed in situ expression in 25 malignant and 13 benign human bone and soft tissue tumours. Reverse transcriptase-polymerase chain reaction analyses confirmed mRNA expression of FAP and DPP-IV in all individuals. Immunohistochemistry using pre-fixed frozen sections revealed that FAP was positive in low-grade myofibroblastic sarcoma, the fibroblastic component of osteosarcomas, and malignant fibrous histiocytomas, but negative in Ewing’s sarcomas and rhabdomyosarcomas. DPP-IV showed similar immunohistochemical results. Among benign tumours, non-ossifying fibromas, desmoid tumours and chondroblastomas expressed both FAP and DPP-IV. Giant cells expressed DPP-IV in giant cell tumours. CONCLUSIONS: Our data suggest that FAP and DPP-IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy. DPP-IV is also expressed in monocyte–macrophage lineage cells.