Calcifying Cystic Odontogenic Tumour: immunohistochemical expression of matrix metalloproteinases, their inhibitors (TIMPs and RECK) and inducer (EMMPRIN).
BACKGROUND
Calcifying cyst odontogenic tumour (CCOT) is a rare benign cystic neoplasm of odontogenic origin. MMPs are responsible for extracellular matrix remodelling and, together their inhibitors and inducer, determinate the level of its turnover in pathological processes, leading to an auspicious microenvironment for tumour development. Thus, our goal was to evaluate matrix metalloproteinases (MMPs-2, -7, -9 and -14), their inhibitors (TIMPs-2, -3, -4 and RECK) and its inductor (EMMPRIN) expression in CCOT.


METHODS
We used 18 cases of CCOT submitted to immunolocalization of the target proteins and analysed in both neoplastic odontogenic epithelial and stromal compartments.


RESULTS
All molecules evaluated were expressed in both compartments in CCOT. In epithelial layer, immunostaining for MMPs, TIMPs, RECK and EMMPRIN was found in basal, suprabasal spindle and stellate cells surrounding ghost cells and ghost cells themselves, except for MMP-9 and TIMP-2 which were only expressed by ghost cells. In stromal compartment, extracellular matrix, mesenchymal (MC) and endothelial cells (EC) were positive for MMP-2, -7, TIMP-3 and -4, while MMP-9, TIMP-2 and RECK were positive only in MC and MMP-14 only in EC. Statistical significance difference was found between both compartments for MMP-9 (P < 0.001), RECK (P = 0.004) and EMMPRIN (P < 0.001), being more expressed in epithelium than in stroma. Positive correlation between both stromal EMMPRIN and RECK expression was found (R = 0.661, P = 0.003).


CONCLUSIONS
We concluded that these proteins/enzymes are differentially expressed in both epithelium and stroma of CCOT, suggesting an imbalance between MMPs and their inducer/inhibitors may contribute on the tumour behaviour.
Department of Oral Pathology, Dental School, University of São Paulo, São Paulo, Brazil.
Fábio C
FC
Prosdócimi
Camila O
CO
Rodini
Mari C
MC
Sogayar
Suzana C O M
SC
Sousa
Flávia C A
FC
Xavier
Katiúcia B S
KB
Paiva
D000293:Adolescent; D000328:Adult; D051926:Basigin / Q000032:analysis*; D042783:Endothelial Cells / Q000737:chemistry / Q000201:enzymology; D004848:Epithelium / Q000737:chemistry / Q000201:enzymology; D005109:Extracellular Matrix / Q000737:chemistry / Q000201:enzymology; D005260:Female; D058851:GPI-Linked Proteins / Q000032:analysis*; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000032:analysis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020783:Matrix Metalloproteinase 7 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008648:Mesoderm / Q000737:chemistry / Q000201:enzymology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009808:Odontogenic Tumors / Q000737:chemistry* / Q000201:enzymology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis*; D059016:Tumor Microenvironment; D055815:Young Adult; D000097792:Tissue Inhibitor of Metalloproteinase-4
D051926:Basigin; D058851:GPI-Linked Proteins; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D020782:Matrix Metalloproteinases; D009363:Neoplasm Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C497886:BSG protein, human; C115460:RECK protein, human; C560823:TIMP2 protein, human; C088390:TIMP3 protein, human; C060932:MMP7 protein, human; C522361:MMP2 protein, human; C579270:MMP9 protein, human; C507086:MMP14 protein, human
Calcifying Cystic Odontogenic Tumour; EMMPRIN; RECK; matrix metalloproteinases; tissue inhibitors of MMPs