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Stains

Metalloproteinases (MMP)


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 7 January 2013, last major update January 2013
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

See also MMP1, MMP2, MMP3, MMP9, MMP13 below

Definition
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● Family of neutral zinc metalloenzymes secreted as latent proenzymes, activated by proteolytic cleavage of NH2 terminal domain
● Degrade various extracellular matrix proteins and other molecules (Wikipedia)
● Includes collagenase (degrades collagen types I, II and III), gelatinase (degrades type IV collagen) and stromeolysins
● Imbalance between metalloproteinases and their inhibitors (TIMPs) are associated with tumor degradation of the extracellular matrix
● Also regulate inflammation, epithelial-mesenchymal transition, cell proliferation, angiogenesis, apoptosis, various renal diseases (Am J Physiol Renal Physiol 2012;302:F1351)
● Mediate endometrial matrix remodeling prior to menstruation (J Clin Endocrinol Metab 2012;97:E888)

Uses by pathologists
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● No clinical uses at this time

Micro images
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Immunohistochemical localization of MMP2 (A), MMP3 (B) and MMP9 (C) in normal colon


MMP2 (left) and MMP9 (right) in situ hybridization in colorectal tumor sections


Fig A: MMP2; Fig B: MMP9


MMP1

Definition
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● Matrix metalloproteinase 1
● Also called collagenase1, interstitial collagenase
● Cleaves alpha chains of types I, II and III collagen, apparently facilitating tumor invasion through collagenous stroma
● Expression increased in endothelial cells

Positive staining - disease
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● Colonic carcinoma (stroma and epithelium, Am J Surg Pathol 2002;26:206)


MMP2

Definition
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● Also called type IV gelatinase A
● MMP2 and its inhibitor TIMP2 are secreted independently and complex extracellularly
● Activated by type IV urokinase plasminogen activator when MMP2 or MMP9 are bound to cell surface; degraded by same when MMPs are in soluble form
● Impaired balance in local levels of MMPs and TIMPs causes extracellular matrix degradation during tumor invasion
● MMP2 and MMP9 are upregulated at invasive front of endometrioid endometrial and ovarian endometrioid carcinomas, may degrade basement membrane (Hum Pathol 2011;42:57)

Positive staining - disease
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● Bladder carcinoma (71%)


MMP3

Definition
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● Also called stromeolysin-1


MMP9

Definition
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● Also called type IV gelatinase B
● Bladder carcinoma: 71% of tumor cells are immunoreactive


MMP13

Definition
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● Principal proteinase expressed by stromal cells of giant cell tumor of bone, has role in bone resorption (Hum Pathol 2010;41:1320)


End of Stains > Metalloproteinases (MMP)


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