Differential Expression of Fibroblast Activation Protein-Alpha and Lysyl Oxidase in Subtypes of Ameloblastoma

Author(s): Tim Vangansewinkel, Ronald Driesen, Jimoh Olubanwo Agbaje, Pascal Gervois, Akinyele Olumuyiwa Adisa, Adeola Adenike Olusanya, Juwon Tunde Arotiba, Esther Wolfs, Ivo Lambrichts, Constantinus Politis

Ameloblastomas are benign, mostly intra-osseous, tumours originating from ectodermal odontogenic epithelium and display extracellular matrix remodelling. We determined whether fibroblast activation protein-alpha (FAP-α), a collagenolytic enzyme and lysyl oxidase (LOX), a collagen cross-linker were differentially regulated in ameloblastoma subtypes. Masson’s trichrome staining and immunohistochemistry were performed on human samples from gross mandibular or maxillary ameloblastoma. Co-localization studies in tumorigenic tissue of follicular, plexiform and desmoplastic ameloblastoma showed absence of the mesenchymal cell marker vimentin but high epithelial cell adhesion molecule (EPCAM) expression, an epithelial marker. Strong FAP-α staining was also noted, however, the stellate reticulum of plexiform ameloblastoma contained a higher number of FAP-α positive cells than the follicular subtype. Weak LOX staining was demonstrated in tumorigenic tissue of the follicular subtype but profound reactivity was observed in stromal plexiform and tumorigenic desmoplastic tissue. The desmoplastic staining profile for FAP-α and LOX shared resemblance with the unicystic subtypes. Tumorigenic outgrowths in desmoplastic ameloblastoma were associated with vimentin positive and EPCAM negative cancer-associated fibroblasts suggesting a role in tumour invasion. In conclusion, FAP-α expression in ameloblastoma seems to be involved in tumour growth and invasion whereas LOX expression is differentially regulated in ameloblastoma subtypes offering a new perspective for understanding specific growth patterns of ameloblastoma subtypes.