大肠癌组织中基质金属蛋白酶-9、基质金属蛋白酶抑制剂-1的表达及对微血管生成和肿瘤转移的影响

目的　探讨基质金属蛋白酶 -9(MMP -9)与基质金属蛋白酶抑制剂 -1(TIMP -1)在大肠癌中的表达及其与血管生成 ,侵袭转移之间的关系。方法　采用免疫组化S -P法 ,检测 46例大肠癌组织中MMP -9,TIMP -1的表达和微血管密度之间的关系。结果　MMP -9的表达与肿瘤的分化程度、浸润深度、Dukes分期及淋巴结转移明显相关 (P <0 .0 5或P <0 .0 1) ;TIMP -1的表达与Dukes分期、淋巴结转移明显相关 ( P <0 .0 5或 P <0 .0 1) ;MMP -9表达阳性的大肠癌组织微血管密度 (MVD)值明显高于表达阴性者 (P <0 .0 1)。结论　MMP -9、TIMP -1的表达和微血管生成与大肠癌侵袭转移密切相关     

基质金属蛋白酶和组织金属蛋白酶抑制剂在大肠癌中的表达

目的　研究基质金属蛋白酶 (MMPs)及组织金属蛋白酶抑制剂 (TIMPs)在大肠癌中的表达特点 ,与肿瘤发生发展的关系 ,以及在肿瘤治疗中的应用前景。　方法　采用RT PCR方法测定 2 8例大肠癌患者肿瘤组织和周围正常粘膜的基质金属蛋白酶 2 (MMP 2 )、膜型 1 基质金属蛋白酶 (MT1 MMP)、基质溶素 (MMP 7)、组织金属蛋白酶抑制剂 2 (TIMP 2 )、组织金属蛋白酶抑制剂 3(TIMP 3)的mRNA表达状况 ,并将其结果与临床及病理学资料进行统计学分析。　结果　 (1) 2 7例患者肿瘤组织中MMP 7mRNA表达阳性 ,MMP 2、MT1 MMP、TIMP 2和TIMP 3在肿瘤组织和正常粘膜中均有高表达 ;(2 )肿瘤组织中MMP 7mRNA的表达水平与大肠癌患者的Dukes′分期相关 (P <0 0 1) ;(3)淋巴结阳性患者的肿瘤组织TIMP 2表达水平为 (1 2 5± 0 46 )明显高于淋巴结阴性患者的 (0 75± 0 41) ,差异有显著性意义 (P <0 0 1) ;(4)大肠癌患者癌周正常粘膜TIMP 3mRNA表达随患者Duke′s分期的进展和肿瘤浸润深度的增加而降低 (P <0 0 1) ;(5 )TIMPs与MMPs之间无明显相关关系 (P >0 1)。　结论　MMP 7可望成为诊断大肠癌的敏感指标 ;人工诱导TIMP 2、TIMP 3或阻断MMP 7、MMP 2、MT1 MMP的表达可能抑制肿瘤的浸润和转移 ,成为肿瘤治疗的新途径。     

基质金属蛋白酶-9及其抑制因子在肾细胞癌组织中的表达和意义

目的　探讨基质金属蛋白酶 9(MMP 9)和金属蛋白酶组织抑制因子 1(TIMP 1)在肾细胞癌中的表达及其与临床病理参数之间的关系。方法　采用免疫组织化学链霉菌抗生物素蛋白过氧化酶 (SP)法检测 5 5例肾细胞癌中MMP 9和TIMP 1的表达情况。结果　MMP 9、TIMP 1蛋白在肾细胞癌和正常肾组织中的阳性表达率各为 63 .63 %和 10 .0 0 % (P <0 .0 5 ) ;60 .0 0 %和10 .0 0 % (P <0 .0 5 )。在肾癌中 ,MMP 9蛋白表达与肿瘤Robson分期、肾包膜侵袭和淋巴结转移密切相关 (P <0 .0 5 ) ,而与组织学类型无关 (P >0 .0 5 ) ;TIMP 1蛋白表达与肾细胞癌的临床病理参数无关 (P >0 .0 5 )。结论　MMP 9蛋白高表达参与了肾癌的发展 ,MMP 9和TIMP 1的平衡失调可能在肾癌的侵袭转移中发挥重要作用。     

MMP-2和TIMP-2蛋白在乳腺癌组织中的表达及其与肿瘤转移的关系

为探讨乳腺肿瘤组织中细胞外基质金属蛋白酶 -2 (MMP 2 )和组织基质金属蛋白酶抑制剂 -2 (TIMP 2 )的表达情况 ,研究及其与乳腺肿瘤发生、发展中的生物学意义并观察其与乳腺癌浸润及转移的相关性 ,作者采用免疫组化方法检测 5 8例乳腺浸润性导管癌及 2 0例乳腺纤维腺瘤的组织标本中MMP 2和TIMP 2的表达情况并进行对比观察。结果示 5 8例乳腺癌和 2 0例乳腺纤维腺瘤的组织中MMP 2的表达分别为 43 .1%(2 5 / 5 8)和 10 %(2 / 2 0 ) ;TIMP 2的表达分别为 5 5 .17%(3 2 / 5 8)和 90 %(18/ 2 0 )。MMP 2的高表达与肿瘤的病理分级、淋巴结转移呈正相关 ,TIMP 2阳性表达与肿瘤的病理分级、淋巴结转移呈负相关。提示MMP 2和TIMP 2的表达与乳腺癌的浸润和淋巴结转移密切相关 ,MMP 2阳性表达率上升和 /或TIMP 2阳性表达率下降 ,表示乳腺癌浸润及转移能力增强 ,联合检测两指标有助于乳腺癌浸润转移和预后的判断。     

检测金属基质蛋白酶及其抑制物对判断膀胱癌浸润和转移的意义

目的　探讨金属基质蛋白酶 (MMP)及其抑制物检测在判断膀胱癌恶性度及预后中的作用。　方法　采用Westernblot和RT PCR方法 ,检测人膀胱肿瘤组织中MMP 2、MMP 9、TIMP 2蛋白表达和MMP 2、TIMP 2基因表达 ,应用计算机图像分析测定表达电泳条带的吸光度A值。　结果　膀胱肿瘤组织MMP 2、MMP 9、TIMP 2蛋白与基因表达与正常膀胱组织比较 ,差别有显著性意义 (P <0 .0 1) ;膀胱肿瘤组织TIMP 2蛋白与基因的吸光度A平均值与正常膀胱组织比较 ,差别无显著性意义 (P >0 .0 5 )。表浅膀胱癌组织的MMP 2 /TIMP 2蛋白、基因吸光度A平均值比率与正常膀胱组织比较 ,差别有显著性意义 (P <0 .0 5 ) ;浸润性膀胱癌的MMP 2 /TIMP 2蛋白、基因吸光度A平均值比率与正常膀胱组织相比 ,差别有显著性意义 (P <0 .0 1)。G2 、G3 与G1的MMP 2 /TIMP 2平均吸光度A值比率差别有显著性意义 (P <0 .0 1)。　结论　MMP 2、MMP 9表达和MMP 2 /TIMP 2比率对判断膀胱肿瘤浸润及转移有一定意义。检测MMP 2 /TIMP 2比率失衡较单纯检测MMP 2、TIMP 2的蛋白与基因表达更有意义     

基质金属蛋白酶－9、细胞金属蛋白酶抑制因子－1在胃癌中的表达

目的：探讨基质金属蛋白酶－9（MMP－9）,组织金属蛋白酶抑制因子－1（TIMP－1）在胃癌中表达的意义。方法：采用免疫组化S－P法对47例胃癌组织进行MMP－9及TIMP－1的检测。结果：MMP－9,TIMP－1主要表达于癌周基质细胞,癌细胞少量表达,MMP－9,TIMP－1表达与胃癌患淋巴结转移（P＜0．01）,浆膜浸润相关（P＜0．01）;TIMP－1的表达与胃癌TNM分期相关（P＜0．05）,而MMP－9的表达与胃癌TNM分期无相关性（P＞0．05）。结论：MMP－9及TIMP－1可作为判断胃癌恶性行为的重要生物学标记物。     

胰腺癌基质调节蛋白表达与肥大细胞计数的相关性研究

目的研究胰腺癌组织中细胞外基质金属蛋白酶诱导因子(EMMPRIN)、基质金属蛋白酶1(MMP1)、MMP9及金属蛋白酶组织抑制因子1(TIMP1)的表达和肥大细胞计数(MCC),并探讨其临床病理意义及其相关性。方法51例胰腺癌手术切除标本,经10%甲醛固定后常规制作石蜡包埋切片,行ABC免疫组化染色。结果胰腺癌组织中EMMPRIN、MMP1、MMP9和TIMP1表达阳性率分别为56.9%、54.9%、60.8%和49.0%,其评分值分别为(2.5±1.5)分、(2.3±1.9)分、(2.4±1.6)分和(1.9±1.6)分。高分化腺癌和无转移癌的前三项指标的阳性率及其评分值明显低于低分化腺癌和转移癌,中分化腺癌(除MCC及MMP9评分值外)上述指标亦明显低于低分化癌,而TIMP1则相反,其差异均有统计学意义(P<0.05,P<0.01)。胰腺癌组织中MCC平均值为(16.1±6.8)个/HP,高分化腺癌和无转移癌的MCC明显低于低分化腺癌和转移癌(P<0.01)。EMMPRIN、MMP1和MMP9阳性病例及TIMP1阴性病例的MCC明显高于EMMPRIN、MMP1、MMP9阴性病例及TIMP1阳性病例(P<0.01)。MCC与EMMPRIN、MMP1及MMP9评分值呈正相关,与TIMP1评分值呈负相关;EMMPRIN、MMP1和MMP9评分值之间均呈正相关,但与TIMP1评分值之间均呈负相关。结论MCC和EMMPRIN、MMP1、MMP9及TIMP1的表达均是反映胰腺癌进展和预后的重要标记物,它们可能相互影响和共同调节胰腺癌侵袭和转移发生的潜力。     

组织蛋白酶-D和nm23-H1蛋白表达与结直肠癌浸润、转移的关系

目的　通过检测组织蛋白酶 D(CathpsinD ,Cat D)和nm 2 3 H1在结直肠癌中表达情况 ,探讨组织蛋白酶 D和nm 2 3 H1蛋白表达与大肠癌浸润和转移的关系。方法　采用SP免疫组织化学方法检测 74例结直肠癌标本中Cat D和nm 2 3 H1的表达情况 ,并分析其与大肠癌的临床病理特征及肿瘤浸润、转移的相关性。结果　本组病例中Cat D的阳性表达率为 70 .3 % ,Cat D阳性组的术后复发转移率高于Cat D阴性组 ( P <0 .0 5 ) ,Cat D过度表达与结直肠癌的浸润深度、淋巴结转移相关 (P <0 .0 5 )。nm2 3 H1低表达与结直肠癌淋巴结转移及术后复发转移相关 (P <0 .0 5 )。结论　Cat D和nm 2 3 H1均与结直肠癌的浸润转移密切相关 ,术前联合检测两者对临床预测结直肠癌患者有无淋巴结转移及术后复发转移的可能性 ,有一定的提示作用。     

壶腹癌MMP-9、TIMP-1的表达及其与淋巴结转移的相关性研究

目的：探讨基质金属蛋白酶9（MMP－9）、组织金属蛋白酶抑制因子－1在壶腹癌中表达的意义。方法：采用免疫组化S－P法对32例壶腹癌组织进行MMP－9、TIMP－1的检测。结果：MMP－9、TIMP－1在壶腹癌组织中阳性表达率分别为65．6％（21／32），46．9％（15／32），MMP－9的表达与壶腹癌患者淋巴结转移呈正相关（P＜0．05），而TIMP－1的表达则相反，MMP－9和TIMP－1的表达呈负相关（P＜0．01）。结论：MMP－9可作为判断壶腹癌恶性生物学行为的标记物。人工诱导TIMP－1的表达可能抑制肿瘤的浸润和转移，为肿瘤治疗提供了新的方向。     

JAK2激酶抑制剂AG490对胃癌细胞侵袭的影响

目的　观察JAK2激酶抑制剂AG4 90对胃癌细胞侵袭以及对基质金属蛋白酶类(MMPs)、组织型基质金属蛋白酶抑制物 (TIMPs)表达的影响 ,探讨STAT3信号转导通路在胃癌侵袭转移调控中的作用。方法　应用JAK2激酶抑制剂AG4 90处理胃癌BGC 82 3细胞 ,Matrigel肿瘤体外侵袭模型检测肿瘤细胞侵袭 ;Westernblot检测STAT3、MMP 2、MMP 9蛋白表达及活性 ;RT PCR检测MMPs、TIMPsmRNA的表达。结果　AG4 90可抑制JAK2 /STAT3信号转导通路活化及胃癌BGC 82 3细胞侵袭 ,在此过程中AG4 90在mRNA和蛋白水平抑制MMP 2和MMP 9表达 ,同时上调TIMP 1、TIMP 2mRNA的表达。结论　STAT3信号转导通路参与胃癌细胞侵袭调控 ,阻断STAT3通路活化可以抑制胃癌细胞侵袭 ,这一作用可能是通过抑制MMP 2和MMP 9表达以及上调TIMP 1和TIMP 2表达实现的。     

MMP-9、TIMP-1在膀胱癌中的表达及其与浸润转移的关系研究

目的研究MMP-9和TIMP—1在膀胱癌中的表达情况,探讨其表达失衡与膀胱癌转移和预后的关系。方法应用S—P免疫组化法,检测86例膀胱癌MMP-9和TIMP—1表达情况,并行回顾性随访。结果在68例膀胱癌组中,MMP-9、TIMP-2阳性表达率分别为63．95％、59．30％。MMP-9阳性表达率随着肿瘤病理分级、浸润深度、淋巴结转移、TNM分期的升高而增加,而TIMP—1阳性表达率则呈下降趋势（P〈0．05）。MMP-9表达超过TIMP—1者膀胱癌发生肌层浸润、淋巴结转移的比例明显高于TIMP—1表达超过MMP-9者或二者表达平衡者,而MMP-9表达超过TIMP—1者生存率明显低于TIMP-1表达超过MMP-9者（P〈0．05）。结论MMP-9以促进肿瘤浸润转移为主,TIMP—1对膀胱癌有独立的抑制作用,MMP-9阳性表达而TIMP—1阴性表达者则其膀胱癌预后不良。MMP-9、TIMP—1表达可作为判断膀胱癌生物学行为和预后的重要指标。     

Role of MMP-9 and its tissue inhibitor TIMP-1 in human osteosarcomaFindings in 42 patients followed for 1–16 years

Background?The activity of matrix metalloproteinases (MMPs) in degrading extracellular matrix is controlled by activation of proenzymes and inhibition of MMP tissue inhibitors (TIMPs). Patients and methods?To assess the proteolytic cascade imbalance in malignancy progression, tissue expression and serum levels of MMP-2, MMP-9 and of their inhibitors TIMP-2 and TIMP-1 respectively were evaluated in 42 selected patients with high-grade osteosarcoma (OS). MMP-2, MMP-9, TIMP-2 and TIMP-1 were studied in biopsies by immunohistochemistry and in serum by ELISA test. Patients were subdivided into 3 groups according to their follow up: continuously disease-free, diagnosis of metastasis during follow-up, and metastasis at diagnosis. Results?Immunohistochemistry demonstrated an imbalance between MMPs and TIMPs, with a more evident role for MMP-9 than for MMP-2 in tumor progression. TIMP-1 inhibitor in plasma was higher in patients with osteosarcoma than in a control group. This high value of TIMP-1 was particularly evident in the group of patients who later developed metastases and/or local recurrences, and in those with metastases at diagnosis. Interpretation?Our findings confirm the protective action of TIMP-1, as MMP inhibitor, but also show its activity as a growth factor underlining its multifunctional role in OS.     

Role of MMP-9 and its tissue inhibitor TIMP-1 in human osteosarcoma: findings in 42 patients followed for 1-16 years

BACKGROUND: The activity of matrix metalloproteinases (MMPs) in degrading extracellular matrix is controlled by activation of proenzymes and inhibition of MMP tissue inhibitors (TIMPs). PATIENTS AND METHODS: To assess the proteolytic cascade imbalance in malignancy progression, tissue expression and serum levels of MMP-2, MMP-9 and of their inhibitors TIMP-2 and TIMP-1 respectively were evaluated in 42 selected patients with high-grade osteosarcoma (OS). MMP-2, MMP-9, TIMP-2 and TIMP-1 were studied in biopsies by immunohistochemistry and in serum by ELISA test. Patients were subdivided into 3 groups according to their follow up: continuously disease-free, diagnosis of metastasis during follow-up, and metastasis at diagnosis. RESULTS: Immunohistochemistry demonstrated an imbalance between MMPs and TIMPs, with a more evident role for MMP-9 than for MMP-2 in tumor progression. TIMP-1 inhibitor in plasma was higher in patients with osteosarcoma than in a control group. This high value of TIMP-1 was particularly evident in the group of patients who later developed metastases and/or local recurrences, and in those with metastases at diagnosis. INTERPRETATION: Our findings confirm the protective action of TIMP-1, as MMP inhibitor, but also show its activity as a growth factor underlining its multifunctional role in OS.     

Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer

Previous studies have detected high levels of matrix metalloproteinases (MMPs) in metastatic prostate cancer. In this study, we recruited 40 patients with prostate cancer (PCa): 20 presented organ-confined carcinoma and 20 had metastatic cancer. We also recruited 40 subjects for control groups, 20 with benign prostate hyperplasia (BPH) and 20 healthy males with similar characteristics. All of the patients were monitored at the beginning (time 0) and after 90 days. We analyzed the plasma concentrations of MMP-2, MMP-9, MMP-13, TIMP-1 and the enzyme activity of MMP-2 and MMP-9,using specific ELISA tests. The plasma concentrations of MMP-2, MMP-9 and MMP-13 were higher in PCa patients with metastasis than in the other groups, and in these patients decreased markedly after therapy began. For MMP-2 and MMP-9, greater differences were observed in enzyme activity than in plasma concentrations. TIMP-1 was reduced in PCa patients with metastasis, even if the intergroup differences were not statistically significant. Our results suggest that the plasma concentration and activity of MMPs, in association with PSA determination, could play a role in diagnosis, monitoring therapy and evaluating malignant progression in PCa.     

膀胱癌组织MMP-9和TIMP-1的表达及其意义

目的　研究金属蛋白酶 9(MMP 9)及其抑制因子 (TIMP 1)在膀胱癌中的表达及其临床意义。方法　应用免疫组化方法检测MMP 9及TIMP 1在 6 5例膀胱癌和 19例非肿瘤性膀胱组织中的表达。结果　MMP 9在膀胱癌细胞和间质组织中均有表达 ,而TIMP 1主要表达在膀胱癌细胞中 ,在间质组织中很少表达。TIMP 1在膀胱癌细胞中的表达低于非肿瘤性膀胱组织中移行上皮的表达 ,两者差别有统计学意义 (P <0 .0 5 ) ,但与膀胱癌的病理分级、分期无统计学相关性 (P >0 .0 5 )。MMP 9在膀胱癌细胞及间质中的表达均高于非肿瘤性膀胱组织 ,两者差别有统计学意义 (P <0 .0 5 ) ,而且与膀胱癌的病理分级、分期均呈正相关 (P <0 .0 5 )。膀胱癌细胞表达TIMP 1与间质组织表达MMP 9呈负相关 (P <0 .0 5 ) ,MMP 9及TIMP 1的表达与肿瘤的复发、多发均无相关性 (P >0 .0 5 )。结论　MMP 9和TIMP 1参与膀胱癌的浸润和转移 ,对预后判断、诊断及治疗具有一定的意义。     

骨桥蛋白、神经性-钙粘附素和MMP-9在结直肠癌中的表达及意义

目的探讨骨桥蛋白(OPN)、神经性-钙粘附素(N-cadherin)和明胶酶(MMP-9)在结直肠癌中的表达及意义。方法选取2012年8月至2015年8月诊治的98例结直肠癌患者,采用免疫组织化学两步法检测OPN、N-cadherin和MMP-9在结直肠癌组织中的表达。采用SPSS20.0统计学软件处理数据。OPN、N-cadherin、MMP-9的阳性表达率与临床病理指标的关系采用χ~2检验,P0.05表示差异具有统计学意义。结果在98例结直肠癌患者中OPN阳性表达60例(61.2%);N-cadherin阳性表达35例(35.7%);MMP-9阳性表达占60例(61.2%)。三者阳性表达率与结直肠癌患者的性别、年龄大小、肿瘤大小均无统计学意义,而与患者浸润深度、肝脏转移、淋巴结转移差异均具有统计学意义(P0.05)。结论 OPN、N-cadherin和MMP-9的表达与结直肠癌有密切关系,在其发生、发展过程中具有协同作用。     

MMP-2和TIMP-2在大肠癌组织中的表达及其意义

目的探讨基质金属蛋白酶-2(MMP-2)和组织基质金属蛋白抑制剂-2(TIMP-2)在大肠癌组织中的表达及其意义。方法应用免疫组织化学SP法对60例大肠癌组织MMP-2和TIMP-2表达情况进行检测。结果MMP-2和TIMP-2在大肠癌组织中表达的阳性率分别为64.3%和30.3%。MMP-2的表达与大肠癌的病理分期和淋巴转移呈正相关(P<0.05),而TIMP-2的表达与其呈负相关,MMP-2和TIMP-2的表达呈负相关(P<0.05)。结论MMP-2和TIMP-2的表达与大肠癌的病理分期和淋巴转移密切相关,可作为判断大肠癌生物学行为的参考指标。     

Serum matrix metalloproteinases MMP-2 and MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in diabetic nephropathy

BACKGROUND: The regulation of mesangial extracellular matrix (ECM) turnover engages a number of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). High glucose concentration affects ECM degradation and the activities of MMPs and TIMPs. ECM accumulation is involved in the pathogenesis of diabetic nephropathy. METHODS: Serum MMP-9, MMP-2, TIMP-2 and TIMP-1 were measured with ELISA in patients with either chronic renal failure (CRF, n=20), type 2 diabetes mellitus (DM2, n=16) or diabetic nephropathy (DM2+CRF, n=14), and healthy controls (n=20). RESULTS: Diabetic nephropathy was related with profound decrease of serum TIMP-2 (122.2 +/- 47.2 vs. 263.0 +/- 89.2 ng/mL), TIMP-1 (242.5 +/- 96.9 vs. 347.4 +/- 87.2 ng/mL) and MMP-2 (385.4 +/- 42.6 vs. 517.2 +/- 75.4 ng/mL) (p<0.001). Both TIMP-1 and TIMP-2 were reduced in diabetic nephropathy in comparison with either diabetes alone (p<0.01 and p<0.001; respectively) or CRF alone (p<0.001 for both). An approximately 2-fold increase of MMP-9/TIMP-1 and MMP-2/TIMP-2 ratio was found in diabetic nephropathy when compared with diabetes with normal renal function (p<0.01). Further, in DM2 patients, TIMP-2 was decreased when compared with CRF alone (219.2 +/- 71.8 vs. 296.8 +/- 58.4 ng/mL). MMP-2 was lowered in both groups of DM2 and CRF patients (413.8 +/- 59.0 ng/mL and 409.7 +/- 93.1 ng/mL, vs. normal control value of 517.2 +/- 75.4 ng/mL; p<0.001). CONCLUSIONS: These data indicate that circulating TIMP-1, TIMP-2 and MMP-2 are decreased in patients with diabetic nephropathy when compared with either CRF or diabetes.     

Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue

Matrix metalloproteinases (MMPs) have been implicated in progression and metastases of different tumours. The balance between the MMPs and their natural inhibitors (tissue inhibitors of matrix metalloproteinases; TIMP) seems to be an important factor related to this role. Here, the expression of MMP-2 and -9 along with TIMP-1 and -2 was examined in prostate cancer tissue. A total of 40 radical prostatectomy specimens were embedded in paraffin and immunohistochemical staining was performed to detect MMP-2 and -9, and TIMP-1 and -2. The immunoreactivity was assessed semiquantitively using routine light microscopy. The intensity of staining was correlated to preoperative PSA, T category, Gleason score and clinical parameters of the specimens. The imbalance of MMPs and TIMPs was recognised as a significant loss of TIMP-1 in malignant epithelium and an upregulation of MMPs. Palpable tumours (T2, T3) expressed significantly more MMP-2 and significantly less MMP-9 than T1c tumours. Our data are in accordance with other literature reports in that an imbalance of MMPs and TIMPs is found in malignant tumours. The observed imbalance of MMP and TIMP is mainly caused by a loss of TIMP-1. Furthermore, palpable tumours demonstrated significantly more MMP-2 and significantly less MMP-9 expression than nonpalpable tumours.