演講人：陳玉昆副教授 高雄醫學大學附設醫院口腔病理科主任 暨主治醫師 日 期： 2010 年 12 月 24 日 地 點：第一教學大樓 B1 演藝廳

Part I ： Case report-Mandibular aneurysmal bone cyst Part II ： Case report-Pleomorphic adenoma with extensive necrosis Part II ： Experimental study-Ameloblastoma Content

Part I Chin Dent J 1990;19:33-41 Aneurysmal bone cyst of the mandible – a case report Yuk-Kwan Chen, Li-Min Lin, Cheng-Chung Lin and Steven Lai Chin Dent J 1990;19:33-41 Aneurysmal bone cyst of the mandible – a case report Yuk-Kwan Chen, Li-Min Lin, Cheng-Chung Lin and Steven Lai

IHC: Factor VIII (-ve staining) +internal control

Citation: 3 times Oral Diseases 2004;10:54-9 Part II

Expression of osteonectin/secreted protein acidic and rich in cysteine (SPARC) and matrix metalloproteinases (MMPs) in ameloblastoma Shen, Ling-Chang Chen, Yuk-Kwan Shaw, Shyh-Yu Part III

Ameloblastoma/ 釉質母細胞瘤 Odontogenic epithelial origin The most common clinically significant odontogenic tumor (59.3%~63.2%) A locally aggressive neoplasm Surgery High recurrent rate (50-90%) Contemporary oral and maxillofacial pathology 1997,

SPARC Secreted Protein Acidic and Rich in Cysteine Osteonectin/BM-40/43-kd protein Bone-specific protein linking mineral to collagen Multifunctional glycoprotein (tissue differentiation, embryo development) Modulate cell-matrix interactions and cell function Re-appear in response to tissue injury, inflammation, and remodeling, as well as in tumor growth and metastasis Termine et al. Cell 1981;26:99-105, FASEB J 8:163-73, 1994, Matrix biology 2000;19:

Tissue specific of SPARC in tumors Tumor enhancerDescription GliomaEnhances invasion (migration) MelanomaPromotes metastasis (proliferation and migration) Non small cell lung cancerFavors invasion and migration Invasive meningiomasDiagnostic marker (negative in benign/non-invasive type) Tumor suppressorDescription Ovary carcinomaInduces apoptosis Pancreatic carcinomaTarget for aberrant methylation Breast cancer cellsInhibits proliferation (MDA-MB-231) NeuroblastomaInhibits angiogenesis Role is not the same in different tumors Int J Cancer: 2006;118, Journal of cellular biochemistry 2004;92: Colorectal carcinomaTumor-associated blood vessels

Matrix metalloproteinases (MMPs) Six subfamilies Zinc- and calcium-dependent enzymes that degrade native and denatured collagen and other extracellular components Rise rapidly when tissues undergo remodeling, such as in inflammation, wound healing, and cancer Gelatinase, MMP-2 and -9, are essential proteases for basement membrane-invasive events (nonfibrillar collagen type IV) Circ Res 2003; 92:827-39, modified

Invasion of the surrounding tissue Gene Therapy 2006;13:464–77 MMPs Angiogenesis switch

Matrix metalloproteinases (MMPs) in the invasiveness of ameloblastoma Histopathology 2004;45:65–72 Bone Neoplasm Bone Neoplasm (a) Mitogens (b) Mitogens MMPs (1,2,9) MMPs (c) MMPs induce bone resorption and release of mitogens from the bone matrix (d) Mitogens induce proliferation of ameloblastoma cells as cords branching out from the central portions of the neoplasm

SPARC and MMPs SPARC expression in human melanoma cells directly correlated with MMP-2 and MMP-9 levels and activity SPARC induces MMP-2 activation in human breast cancer cell line Both SPARC and MMP-9 have impact on ECM deposition and angiogenesis in the tumor microenvironment Nature medicine 1997;3,171-5,, Cancer research 1998;58, , Experimental biology and medicine online April 29,2008 Nature medicine 1997;3,171-5,, Cancer research 1998;58, , Experimental biology and medicine online April 29,2008

AIMS To verify the pathologic expression of SPARC in ameloblastoma To establish the association between the presence of SPARC and MMPs in a cohort of ameloblastoma patients.

IHC expression of MMP-1, -2, -9 and SPARC MMP-1 MMP-2 MMP-9 SPARC

Immunohistochemical reactivity Immunoreactivity for SPARC, MMP-1, MMP-2 & MMP-9 was evaluated and classified into four groups: score 0-2  (+) score 3-5  (++) score 6-8  (+++) score 9-12  (++++) Pearson’s χ 2 -test. P -values less than 0.05 were considered to indicate statistical significance Am J Pathol 1996;149,: , modified

Case no.SPARCMMP-1MMP-2MMP-9 1* * * * Case no.SPARCMMP-1MMP-2MMP * * * Immunohistochemical reactivity 1. 在 ameloblastoma tissue 當中，的確有 SPARC 的不正常表現 2. 不同的 sample 之間，同一個蛋白質，有不同的表現強度；同一個 sample 的不同蛋白質，也有不同表現強度

SPARCMMP-1MMP-2MMP-9 SPARC * MMP MMP MMP * Associations between the immunoscores of SPARC, MMP-1, -2 and -9

IHC of MMP-9 and SPARC MMP-9 SPARC

Co-expression of SPARC and MMP-9 ( Double stain IHC) MMP-9 SPARC Co- expression A BC

Conclusion I First to identify the pathologic expression of SPARC in ameloblastoma tissues SPARC was elevated consistently in matched MMP-9 expression

SPARC protein MMP-9 VEGF Angiogenesis Expression in Ameloblastoma Tumor Invasion Pinheiro et al, 2004 Kumamoto et al, 2002 Heissig et al, 2002 Framson & Sage, 2004 Kato et al, 2001 J Oral Pathol Med 2010;39:242-9 Conclusion II : Putative association between SPARC and MMP-9 in ameloblastoma

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