Fasn Expression, Angiogenesis And Lymphangiogenesis In Central And Peripheral Giant Cell Lesions

Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) are non-neoplastic proliferative processes of the jaws. PGCL is a reactive process induced by irritant local factors and CGCL is an intra-osseous lesion of unknown etiology. Both lesions exhibit similar histologic features showing abundant mononuclear cells, admixed with a large number of multinucleated giant cells and a rich vascularized stroma with extravasated erythrocytes, hemosiderin deposition, and blood-filled pools. Recent studies have linked fatty acid synthase (FASN) with angiogenesis. Objective: To evaluate angiogenesis and lymphangiogenesis and their relationship with FASN expression in CGCL and PGCL. Material and Methods: Thirteen CGCL and 14 PGCL of the jaws were selected for immunoexpression of FASN; CD34 and CD105 (to assess blood microvessel density [MVD] and microvessel area [MVA]); and D2-40 (to assess lymphatic MVD and MVA). Results: Within PGCL and CGCL, MVD-CD34 was significantly higher than MVD-CD105, followed by MVD-D2-40. Moreover, a significantly higher number of FASN-positive multinucleated giant cells than mononuclear cells were observed. Between PGCL and CGCL, only MVD-CD34 and all MVA were significantly higher in PGCL. Positive correlation between MVA-CD105 with FASN-positive mononuclear cells in both lesions was observed. Conclusions: Our results show both lesions exhibiting similar levels of FASN expression and neoangiogenesis, suggesting constitutive processes that regulate tissue maintenance.222131137Abbas, N.F., El-Sharkawy, L.S., Abbas, E.A., El-Shaer, A.M.M., Immunohistochemical study of p53 and angiogenesis in benign and preneoplastic oral lesions and oral squamous cel carcinoma (2007) Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 103 (3), pp. 385-390Alö, P.L., Visca, P., Framarino, M.L., Botti, C., Monaco, S., Sebastiani, V., Immunohistochemical study of fatty acid synthase in ovarian neoplasms (2000) Oncol Rep, 7 (6), pp. 1383-1388Andrade, B.A., León, J.E., Carlos, R., Delgado-Azañero, W., Mosqueda-Taylor, A., Graner, E., Expression of fatty acid synthase (FASN) in oral nevi and melanoma (2011) Oral Dis, 17 (8), pp. 808-812Browne, C.D., Hindmarsh, E.J., Smith, J.W., Inhibition of endothelia cell proliferation and angiogenesis by orlistat, a fatty acid synthase inhibitor (2006) FASEB J, 20 (12), pp. 2027-2035Cardoso, S.V., Souza, K.C., Faria, P.R., Eisenberg, A.L., Dias, F.L., Loyola, A.M., Assessment of angiogenesis by CD105 antigen in epithelia salivary gland neoplasms with diverse metastatic behavior (2009) BMC Cancer, 9, p. 391Cheifetz, S., Bellön, T., Calé, C., Vera, S., Bernabeu, C., Massagué, J., Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells (1992) J Biol Chem, 267 (27), pp. 19027-19030Chirala, S.S., Wakil, S.J., Structure and function of animal fatty acid synthase (2004) Lipids, 39 (11), pp. 1045-1053Chuong, R., Kaban, L.B., Kozakewich, H., Perez-Atayde, A., Centra giant cell lesions of the jaws: A clinicopathologic study (1986) J Ora Maxillofac Surg, 44 (9), pp. 708-713Davey, K.J., Perrier, S., Ohe, G., Gilbert, A.D., Bankfalvi, A., Saunders, W.P., Assessment of vascularity as an index of angiogenesis in periradicular granulomas: Comparison with oral carcinomas and normal tissue counterparts (2008) Int Endod J, 41 (11), pp. 987-996Dewsnup, N.C., Susarla, S.M., Abulikemu, M., Faguin, W.C., Kaban, L.B., August, M., Immunohistochemical evaluation of giant cell tumors of the jaws using CD34 density analysis (2008) J Oral Maxillofac Surg, 66 (5), pp. 928-933Flörez-Moreno, G.A., Henao-Ruiz, M., Santa-Sáenz, D.M., Castañeda-Peläez, D.A., Tobön-Arroyave, S.I., Cytomorphometric and immunohistochemical comparison between central and periphera giant cell lesions of the jaws (2008) Oral Surg Oral Med Oral Pathol Ora Radiol Endod, 105 (5), pp. 625-632Gadbail, A.R., Hande, A., Chaudhary, M., Nikam, A., Gawande, M., Patil, S., Tumor angiogenesis in keratocystic odontogenic tumor assessed by using CD-105 antigen (2011) J Oral Pathol Med, 40 (3), pp. 263-269Kahn, H.J., Marks, A., A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors (2002) Lab Invest, 82 (9), pp. 1255-1257Lima, S.C., Rizo, V.H., Silva-Sousa, Y.T., Almeida, L.Y., Almeida, O.P., León, J.E., Immunohistochemical evaluation of angiogenesis and tryptase-positive mast cell infiltration in periapical lesions (2011) J Endod, 37 (12), pp. 1642-1646Matos, F.R., Moraes, M., Nonaka, C.F., Souza, L.B., Almeida, F.R., Immunoexpression of TNF-a and TGF-ß in central and periphera giant cell lesions of the jaws (2012) J Oral Pathol Med, 41 (2), pp. 194-199Matos, F.R., Nonaka, C.F., Miguel, M.C., Galväo, H.C., Souza, L.B., Freitas, R.A., Immunoexpression of MMP-9, VEGF, and vWF in centra and peripheral giant cell lesions of the jaws (2011) J Oral Pathol Med, 40 (4), pp. 338-344Palomba, A., Gallo, O., Brahimi, A., Franchi, A., Evaluation of lymphangiogenesis in premalignant conditions of the head and neck mucosa (2010) Head Neck, 32 (12), pp. 1681-1685Peacock, Z.S., Jordan, R.C., Schimidt, B.L., Giant cell lesion of the jaws: Does the level of vascularity and angiogenesis correlate with behavior? (2012) J Oral Maxillofac Surg, 70 (8), pp. 1860-1866Pizer, E.S., Jackisch, C., Wood, F.D., Pasternack, G.R., Davidson, N.E., Kuhajda, F.P., Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells (1996) Cancer Res, 56 (12), pp. 2745-2747Rossi, S., Graner, E., Febbo, P., Weinstein, L., Bhattacharya, N., Onody, T., Fatty acid synthase expression defines distinct molecular signatures in prostate cancer (2003) Mol Cancer Res, 1 (1), pp. 707-715Seguin, F., Carvalho, M.A., Bastos, D.C., Agostini, M., Zecchin, K.G., Alvarez-Flores, M.P., The fatty acid synthase inhibitor orlistat reduces experimental metastases and angiogenesis in B16-F10 melanomas (2012) Br J Cancer, 107 (6), pp. 977-987Silva, S.D., Cunha, I.W., Nishimoto, I.N., Soares, F.A., Carraro, D.M., Kowalski, L.P., Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas (2009) Oral Oncol, 45 (10), pp. l34-139Souza, P.E., Mesquita, R.A., Gomez, R.S., Evaluation of p53, PCNA, Ki-67, MDM2 and AgNOR in oral peripheral and central giant eel esions (2000) Oral Dis, 6 (1), pp. 35-39Spiegelaere, W., Casteleyn, C., van den Broeck, W., Plendl, J., Bahramsoltani, M., Simoens, P., Intussusceptive angiogenesis: A biologically relevant form of angiogenesis (2012) J Vase Res, 49 (5), pp. 390-404Susarla, S.M., August, M., Dewsnup, N., Faquin, W.C., Kaban, L.B., Dodson, T.B., CD34 staining density predicts giant cell tumor clinica behavior (2009) J Oral Maxillofac Surg, 67 (5), pp. 951-956Vasconcelos, M.G., Alves, P.M., Vasconcelos, R.G., Silveira, E.J., Medeiros, A.M., Queiroz, L.M., Expression of CD34 and CD105 as markers for angiogenesis in oral vascular malformations and pyogenic granulomas (2011) Eur Arch Otorhinolaryngol, 268 (8), pp. 1213-1217Vassilopoulos, S.I., Tosios, K.I., Panis, V.G., Vrostsos, J.A., Endothelia cells of oral pyogenic granulomas express eNOS and CD105/ endoglin: An immunohistochemical study (2011) J Oral Pathol Med, 40 (4), pp. 345-351Vered, M., Büchner, A., Dayan, D., Giant cell granuloma of the jawbones: A proliferative vascular lesion? Immunohistochemica study with vascular endothelial growth factor and basic fibroblastic growth factor (2006) J Oral Pathol Med, 35 (10), pp. 613-619Weiss, L., Hoffmann, G.E., Schreiber, R., Andres, H., Fuchs, E., Körber, E., Fatty-acid biosynthesis in man, a pathway of minor importance. Purification, optimal assay conditions, and organ distribution of fatty-acid synthase (1986) Biol Chem Hoppe Seyler, 367 (9), pp. 905-912Zustin, J., Scheuer, H.A., Friedrich, R.E., Podoplanin expression in human tooth germ tissues and cystic odontogenic lesions: An immunohistochemical study (2010) J Oral Pathol Med, 39 (1), pp. 115-12