The role of matrix metalloproteinases in pathogenesis, diagnostics, and treatment of human prostate cancer

Figures & Tables

The TNM classification
T - Primary tumor (stage based on DRE only)
TX - Primary tumor cannot be assessedT0 - No evidence of primary tumorT1 - Clinically inapparent tumor that is not palpableT1a - Tumor incidental histological finding in 5% or less of tissue resectedT1b - Tumor incidental histological finding in more than 5% of tissue resectedT1c - Tumor identified by needle biopsy (because of elevated PSA)T2 - Tumor that is palpable and confined within the prostateT2a - Tumor involves one half of one lobe or lessT2b - Tumor involves more than half of one lobe, but not both lobesT2c - Tumor involves both lobesT3 - Tumor extends through the prostatic capsuleT3a - Extracapsular extension (unilateral or bilateral)T3b - Tumor invades seminal vesiclesT4 - Tumor is fixed or invades adjacent structures other than seminal vesicles: external sphincter, rectum, levator muscles and/or pelvic wall
N - Regional Lymph Nodes
NX - Regional lymph nodes cannot be assessedN0 - No regional lymph node metastasisN1 - Regional lymph node metastasis
M - Distant Metastasis
M0 - No distant metastasisM1 - Distant metastasisM1a - Non-regional lymph nodesM1b - BonesM1c - Other sites
DRE – digital rectal examination; PSA – prostate-specific antigen; TNM – tumor-node-metastasis

Definition
Low-risk	Intermediate-risk	High-risk
PSA < 10 ng/ml, GS < 7 (ISUP grade 1), cT1-2a	PSA 10–20 ng/ml, GS 7 (ISUP grade 2/3), cT2b	PSA > 20 ng/ml, GS > 7 (ISUP grade 4/5), cT2c	any PSAany GS (any ISUP grade)cT3-4 or cN+
Localized			Locally advanced
GS– Gleason score; ISUP – International Society for Urological Pathology; PSA – prostate-specific antigen

Matrix metalloproteinases	Name	Substrates
MMP-1	collagenase 1	collagen type I, II, III, V, VII, VIII, X gelatine, entactin, aggrecan
MMP-2	gelatinase A	collagen type I, IV, V, VII, X, XI, XIV, gelatine, elastin, fibronectin, laminin, aggrecan
MMP-3	stromelysin 1, proteoglycanase	collagen type III, IV, V, IX, X, XI, elastin, laminin, fibronectin, aggrecan, gelatine, proMMP-1, -8, -9
MMP-7	matrilysin, metalloendopeptidase	collagen type IV, X, gelatine, laminin
MMP-8	collagenase 2	collagen type I, II, III, V, VII, VIII, X, proteoglycans, fibronectin
MMP-9	gelatinase B	collagen type IV, V, VII, X, XIV, gelatine, aggrecan, elastin, entactin, fibronectin
MMP-10	stromelysin 2	collagen type III, IV, V, gelatine, casein, elastin, laminin, aggrecan, fibronectin
MMP-11	stromelysin 3	collagen type IV, fibronectin, laminin, aggrecan, casein, gelatine
MMP-12	elastase, macrophage metaloelastase	collagen type IV, elastin, gelatine, fibronectin, vitronectin, laminin
MMP-13	collagenase 3	collagen type I, II, III
MMP-14	MT1-MMP	collagen type III, gelatine, fibronectin, vitronectin, aggrecan, perlecan, laminin, tenascin
MMP-15	MT2-MMP	aggrecan, perlecan, laminin, bronectin, tenascin, nidogen
MMP-16	MT3-MMP	collagen type III, gelatine
MMP-17	MT4-MMP	cytokines precursors
MMP-18	collagenase 4	collagen type I, II, III
MMP-20	enamelysin	amelogenin
MMP-23	CA-MMP	-
MMP-24	MT5-MMP	proMMP-2, -13
MMP-25	MT6-MMP	proMMP-2
MMP-26	matrilysin, endometase	-