淋巴结阴性乳腺癌基质金属蛋白酶-9表达及预后价值

[目的]研究基质金属蛋白酶-9在淋巴结阴性乳腺癌中的表达及预后意义.[方法]对1990～1998年收治的270例淋巴结阴性乳腺癌患者肿瘤标本,用免疫组织化学方法检测肿瘤细胞基质金属蛋白酶-9(MMP-9)的表达.进一步分析基质金属蛋白酶的表达与其他临床病理预后指标的相关性.单因素检测基质金属蛋白酶的表达作为预后指标对无复发生存率和总生存率的重要性.[结果]肿瘤标本MMP-9阳性率为59.6%(161/270),MMP-9的表达与肿瘤病理分级呈正相关(P＜0.05).单因素分析MMP-9阳性表达患者有较低的无复发生存率(P＜0.05),但和总生存率无关.[结论]淋巴结阴性乳腺癌患者MMP-9表达是预后较差的指标.     

基质金属蛋白酶-2和基质金属蛋白酶-9在直肠癌中的表达及其临床意义

 目的　探讨基质金属蛋白酶-2（MMP-2）及基质金属蛋白酶-9（MMP-9）在直肠癌发病机制及转移中的临床意义。方法　用RT-PCR方法检测MMP-2 mRNA、MMP-9 mRNA在正常肠组织以及直肠癌组织中的表达。结果　MMP-2 mRNA、MMP-9 mRNA在正常肠组织中低表达（0.3150±0.1766、0.3050±0.1995）,而其在有转移的直肠癌患者癌组织中的表达明显增强,与正常对照组比较差异有统计学意义。结论　MMP-2、MMP-9在直肠癌患者中高表达,并且其在癌转移中有重要意义。     

基质金属蛋白酶8在乳腺癌中的表达及其临床意义

目的 分析基质金属蛋白酶8（MMP-8）在乳腺癌中的表达及其与各临床病理参数间的关系,评估MMP-8的表达与乳腺癌转移的相关性.方法 收集具有完整临床资料的乳腺浸润性导管癌标本50例及癌旁正常乳腺组织标本20例,采用免疫组织化学染色SP法检测原发灶中MMP-8表达情况.结果 50例乳腺癌组织中MMP-8阳性表达率高于正常乳腺组织标本[68％（34/50）比15％（3/20）,P＜ 0.05].Ⅰ期乳腺癌MMP-8阳性表达率高于Ⅱ、Ⅲ＋Ⅳ期[94％（15/16）、57 ％（13/23）、55％（6/11）,P＜0.05],无淋巴结转移乳腺癌患者MMP-8阳性表达率高于有淋巴结转移者[84％（21/25）比50％（13/25）,P＜0.05].结论 MMP-8的表达与乳腺癌的转移相关,MMP-8可能参与抑制乳腺癌的转移.     

乳腺癌基质金属蛋白酶2的表达及其临床意义

目的 :探讨乳腺癌 mm p2蛋白表达的临床意义。方法 :应用免疫组织化学方法对乳腺癌石蜡标本进行检测 ,并与患者临床病理指标进行分析。结果 :乳腺癌 m mp2蛋白反应阳性率为 4 5 .8% ,与肿瘤大小、腋淋巴结转移呈正相关。结论 :mmp2参与了乳腺癌的发生、发展过程 ,可能是患者预后不良的指标     

基质金属蛋白酶-2及其组织抑制物在宫颈癌中的表达

目的研究基质金属蛋白酶-2(MMP-2)及其组织抑制物(TIMP-2)在宫颈癌中的表达及其与宫颈癌生物学行为的关系.方法采用免疫组化S-P法对57例宫颈癌组织、17例正常宫颈组织MMP-2、TIMP-2进行检测,并进行x2检验及等级相关分析.结果免疫组化结果显示MMP-2、TIMP-2在宫颈癌组织中表达极显著高于正常宫颈组织(P＜0.01).MMP-2、TIMP-2在宫颈癌不同组织学类型中表达无显著性差异(P＞0.05).MMP-2表达随宫颈癌病理分级、临床分期的升高,淋巴结转移的发生而上调,但无显著性差异(P＞0.05).TIMP-2在宫颈癌临床分期Ⅱb～Ⅳ期的阳性表达显著低于Ⅰ～Ⅱa期(P＜0.05),有淋巴结转移者极显著低于无淋巴结转移者(P＜0.01).TIMP-2随病理分级升高其表达下调,但无显著性差异(P＞G.05).TIMP-2与MMP-2的表达显著负相关.结论MMP-2、TIMP-2,尤其是MMP-2/TIMP-2比率失衡在判断宫颈癌侵袭性、估计其预后中有一定意义.     

膜型基质金属蛋白酶-1在乳腺癌中表达的预后价值

目的探讨膜型基质金属蛋白酶-1（MT1-MMP）蛋白在乳腺癌中表达的临床意义。方法采用免疫组织化学方法检测106例乳腺癌患者手术标本中MT1-MMP蛋白的表达;用统计学软件SPSS11．0作为统计分析的工具,MT1-MMP表达与临床病理因子的关系用卡方检验和Pearson等级相关分析检验;预后分析采用Kaplan—Meier检验Cox Regression。结果乳腺癌组织中MT1-MMP蛋白表达阳性率为62．3％,表达强度在不同分期和不同淋巴结转移数目患者间差异有统计学意义且呈正相关（P〈0．050）,在不同大小肿瘤间及在ER、PR和HER-2不同表达的患者间差异无统计学意义。MT1-MMP阴性患者与弱至中度阳性或强阳性患者间的无病生存期比较,MT1-MMP（-）为65．0％,MT1-MMP（＋-＋＋）为27．1％,MT1-MMP（＋＋＋）为27．8％,差异有统计学意义（P〈0．050）。不同MT1-MMP免疫组织化学染色强度患者的7年生存率也明显不同,MT1-MMP（-）为77．5％,MT1-MMP（＋-＋＋）为60．4％,MT1-MMP（＋＋＋）为50．0％,差异有统计学意义（P〈0．050）。根据不同分期和不同淋巴结转移状态分层分析发现,MT1-MMP蛋白不同表达强度的患者预后差异有统计学意义（P〈0．050）;根据不同肿瘤大小的分层分析发现,不同MT1-MMP表达强度的T2期和T4期患者预后差别有统计学意义（P〈0．050）,但T1和T3期患者预后没有差别。多因素分析显示MT1-MMP是有意义的预后因子,MT1-MMP强阳性患者死亡风险增加2倍,弱到中度阳性患者死亡风险增加1．3倍。结论MT1-MMP的表达与乳腺癌侵袭转移有关,MT1-MMP是乳腺癌的预后因子。     

细胞外基质金属蛋白酶诱导因子和基质金属蛋白酶-2在喉癌中的表达

目的　了解细胞外基质金属蛋白酶诱导因子 (EMMPRIN )和基质金属蛋白酶 2 (MMP 2 )在喉癌的表达情况 ,探讨两者表达的关系以及与喉癌浸润和转移的关系。方法　采用免疫组织化学S P法对 47例喉癌和 2 2例正常喉组织中的EMMPRIN和MMP 2的表达情况进行检测。结果　EMMPRIN和MMP 2在喉癌的阳性表达率 (分别为 87.2 %和 91.5 % )明显高于正常喉组织分别为 ( 9.1%和 18.2 % ) ,EMMPRIN和MMP 2的强阳性表达与喉癌的病理分级、临床分期和淋巴结转移情况有关 ;EMM PRIN和MMP 2的表达一致率为 91.5 % ,Kappa值为 0 .614 ,两者表达具有明显的相关性。 结论　EMMPRIN和MMP 2在喉癌有阳性表达 ,表达与喉癌的临床分期和淋巴结转移有关 ,EMMPRIN与MMP 2的产生有密切的关系     

基质金属蛋白酶MMP2表达与乳腺癌转移及预后的关系

目的：探讨乳腺癌MMP2蛋白表达的临床意义。方法：应用免疫组织化学方法对乳腺癌石蜡标本进行检测，并与患者临床病理指标进行分析。结果：乳腺癌MMP2蛋白阳性反应率为45．8％，与肿瘤大小，腋淋巴结转移相关（P＜0．05），MMP2阴性者生存期延长（P＜0．05），结论：MMP2参与了乳腺癌的发生，发展过程，可能是患者预后的不良指标。此结果为临床建立新的乳腺癌预后预测因子提供有价值的信息。     

基质金属蛋白酶及其抑制剂在乳腺癌中的表达及其临床意义

背景与目的:基质金属蛋白酶(matrixmetalloproteinase,MMP)与基质金属蛋白酶组织抑制剂(tissueinhibitorofmatrixmetalloproteinase,TIMP)的表达失平衡在肿瘤侵袭、转移过程中起重要作用,但与乳腺癌预后关系的报道少见。本研究探讨MMP-2、MMP-9和TIMP-1、TIMP-2的表达与乳腺癌侵袭、转移和预后的关系。方法:原位杂交、免疫组化检测66例有临床和随访资料的乳腺癌患者的MMP-2mRNA、TIMP-2mRNA和MMP-2、MMP-9、TIMP-1、TIMP-2蛋白表达。统计学分析采用χ2检验、Kaplan-Meier和Cox多因素回归分析。结果MMP-2mRNA、TIMP-2mRNA和MMP-2、MMP-9、TIMP-1TIMP-2蛋白的阳性表达率分别为66.7%(44/66)、65.2%(43/66)和71.2%(47/66)、68.2%(45/66)、40.9%(2766)、69.7%(46/66),其中MMP-2蛋白与MMP-2mRNAMMP-9蛋白及TIMP-2mRNA与TIMP-2蛋白的表达存在显著性正相关(P<0.01);TIMP-1与MMP-9蛋白表达呈负相关(P<0.01)。有淋巴结转移的乳腺癌中MMP-2、MMP-9蛋白表达显著高于无转移者,但TIMP-2mRNA、TIMP-1蛋白表达显著低于无转移者(P<0.05)。乳腺癌中MMP-2mRNA和MMP-9蛋白表达与肿块大小、生存状况有显著性相关(P0.05),此外,MMP-9蛋白表达与临床分期存在正相关性(P<0.01)。绝经和ER表达阴性患者的MMP-2mRNA表达水平增高(P<0.     

环氧合酶-2和基质金属蛋白酶-9在宫颈癌中的表达及其临床意义

目的研究环氧合酶-2(COX-2)和基质金属蛋白酶-9(MMP-9)在宫颈癌组织中的表达及临床意义。方法采用免疫组化S-P法检测72例宫颈浸润癌(ICC)、16例癌旁正常宫颈上皮(NCE)组织中COX-2和MMP-9的表达,并分析COX-2和MMP-9表达与ICC病理分级、临床分期、间质浸润和淋巴结转移等临床病理特征的关系。结果ICC组织中COX-2和MMP-9的表达显著高于NCE组织,72例ICC中,COX-2阳性表达率为88.9%,MMP-9阳性表达率为94.4%;16例NCE组织中,COX-2阳性表达率为12.5%,MMP-9阳性表达率为43.8%,两组间差异均有统计学意义(P< 0.01)。COX-2表达与ICC的淋巴结转移和间质浸润深度呈正相关(r分别为0.296和0.257)。MMP-9的表达与ICC的临床分期、病理分级呈正相关(r分别为0.329和0.351)。COX-2和MMP-9在宫颈癌组织中的表达强度呈正相关(r=0.297),二者表达的一致率高达86.1%(62/72)。结论COX-2和MMP-9的高表达与宫颈癌的侵袭和发展有关,二者在宫颈癌的细胞增殖、浸润和转移中有协同作用,联合检测二者的表达对于进一步理解宫颈癌的生物学行为和判断预后有一定价值。     

Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma

Twenty-five to thirty percent of patients with node-negative breast cancer are expected to relapse following surgery, therefore great efforts have been made to identify new prognostic markers that could be useful in defining patients for additional therapy. The expression of MMP-2 and MMP-9 has been associated with high potential of metastasis in several human carcinomas including breast cancer. In the present study we examined the prognostic value of immunoreactive MMP-2/MMP-9 protein in 270 consecutive lymph node negative cases who received radical mastectomy or modified radical mastectomy. Among the patients, 211 cases received adjuvant endocrine therapy and/or adjuvant chemotherapy. Using immunohistochemical assay, we found that 56.7% of the resected tumors were positive for MMP-2 whereas 59.6% of the samples were positive for MMP-9. ² test demonstrated a significant direct association between MMP-2 and MMP-9 ( p < 0.001); positive immunostaining of MMP-2 was significantly related to higher tumor grade ( p < 0.001) and larger tumor size ( p=0.012); positive immunostaining of MMP-9 was significantly related to higher tumor grade ( p=0.002). In univariate analysis, using Cox-proportional hazard model we found MMP-2, MMP-9 and the co-expression of MMPs (MMP2/MMP9) were significantly associated with patients' relapse free survival ( p=0.016, 0.015 and 0.013 respectively) but not overall survival ( p=0.122, 0.320 and 0.091 respectively). Log-rank test also showed that MMP-2, MMP-9 or the co-expression of MMP2/MMP9 was unfavorable prognostic factor for relapse free survival but not overall survival. In subgroup analysis, we found MMPs were more prognostic for patients with no adjuvant treatment than for patients with adjuvant therapy. In multivariate analysis, using Cox-proportional hazard model we found co-expression of MMPs, larger tumor size and higher tumor grade were unfavorable for relapse free survival ( p=0.038, 0.007 and 0.015 for each). We concluded that MMP-2 and MMP-2 are unfavorable prognostic factors in breast cancer patients. They might be potential predictive factor for adjuvant systemic therapy. The co-expression of MMP-2 and MMP-9 has significantly prognostic value in node-negative patients.     

The number of tumor-free axillary lymph nodes removed as a prognostic parameter for node-negative breast cancer

Recently, there has been controversy about the relationship between the number of lymph nodes removed and survival of patients diagnosed with lymph node-negative breast cancer. To assess this relationship, 603 cases of lymph node-negative breast cancer with a median of 126 months of follow-up data were studied. Patients were stratified into two groups（Group A, 10 or fewer tumor-free lymph nodes removed; Group B, more than 10 tumor-free lymph nodes removed）. The number of tumor-free lymph nodes in ipsilateral axillary resections as well as 5 other disease parameters were analyzed for prognostic value. Our results revealed that the risk of death from breast cancer was significantly associated with patient age, marital status, histologic grade, tumor size, and adjuvant therapy. The 5- and 10-year survival rates for patients with 10 or fewer tumor-free lymph nodes removed was 88.0% and 66.4%, respectively, compared with 69.2% and 51.1%, respectively, for patients with more than 10 tumor-free lymph nodes removed. For patients with 10 or fewer tumor-free lymph nodes removed, the adjusted hazard ratio（HR） for risk of death from breast cancer was 0.579（95% confidence interval, 0.492-0.687, P 〈 0.001）, independent of patient age, marital status, histologic grade, tumor size, and adjuvant therapy. Our study suggests that the number of tumor-free lymph nodes removed is an independent predictor in cases of lymph node-negative breast cancer.     

Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer

If oesophageal carcinoma is detected in the superficial stage, the prognosis is better than for advanced oesophageal carcinoma. But the factors which predict the prognosis and treatment policy remain unclear. Matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) have been reported to have close associations with tumour invasion and metastasis. In this study, we retrospectively studied the relations between MMP-7 and MMP-9 expression in immunohistochemistry, clinicopathologic factors, and prognosis in 55 superficial oesophageal carcinomas. MMP-7 and MMP-9 expression occurred in 23.6% and 47.3% of the patients, respectively. MMP-7 expression was significantly correlated with the presence of nodal metastasis (P=0.004). MMP-9 expression was significantly correlated with the depth of tumour invasion (P=0.004), lymphatic permeation (P=0.001), nodal metastasis (P=0.049), and pathologic differentiation grade (P=0.003). By the log-rank test, MMP-7 expression and MMP-9 expression on the invasive front were related to the prognosis. In multivariate analysis, MMP-9 expression on the invasive front was an independent prognostic indicator. The combined expression of MMP-7 and MMP-9 may be a good marker for the degree of malignancy of oesophageal cancer and for the presence of lymphatic metastasis.     

Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer

Summary Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) associates with reduced survival in human breast cancer. COX-2 may be directly involved with mammary carcinogenesis, since expression of COX-2 is sufficient for formation of breast tumors in transgenic mice, and COX-2 selective inhibitors can suppress tumorigenesis in rodent models of breast cancer. MMP-2 is an extracellular matrix degrading proteolytic enzyme that bas been linked to invasion and metastasis. A direct link between COX-2 and MMP-2 may exist, since inhibition of COX-2 activity can result in reduction of MMP-2 expression and activity. In this study we analyzed protein expression of COX-2 and MMP-2 in tissue array specimens of 278 invasive breast cancers by immunohistochemistry. Immunopositivity of these two markers was correlated with each other and with various clinicopathological parameters including survival. We found high COX-2 expression in 30% and high MMP-2 expression in 83% of the breast cancer specimens, and there was a positive association between the expression of these two factors (p=0.003). It was especially evident that whenever COX-2 expression was high, MMP-2 expression was almost invariably high (95%). Furthermore, high expression of either COX-2 or MMP-2 associated with decreased disease specific survival when compared with the COX-2 or MPP-2 low group (p=0.026 and p=0.021, respectively). Taken together, our results indicate that expression of COX-2 protein is associated with expression of MMP-2 protein in human breast cancer and that both COX-2 and MMP-2 are markers of poor prognosis in breast cancer.     

Survivin和MMP-7在结肠癌组织中的表达及临床意义

背景与目的：临床发现同一分期的结肠癌患者实行同一方案治疗预后不同,寻找能单独或结合临床病理分期更准确地判断患者预后的指标非常必要。本研究选择有争论的增殖转移相关蛋白生存素（survivin）、基质金属蛋白酶7（matrix metalloproteinase-7,MMP-7）,研究它们与结肠癌患者临床病理参数及预后的关系,为结肠癌的分子病理分期提供理论基础。方法：选取1995年1月至2003年5月在中山大学肿瘤防治中心住院手术的620例有完整随访资料的结肠癌患者临床资料及病理蜡块,应用组织芯片及免疫组化技术检测survivin、MMP-7表达,研究其与结肠癌患者临床病理参数及预后的关系。结果：本组病例survivin表达正常肠黏膜阳性率为0,而癌组织阳性率为41．0％．两者差异有统计学意义（P〈0．001）。MMP-7表达正常肠黏膜阳性率为40．9％,而癌组织阳性率为88．8％,两者差异有统计学意义（P〈0．05）。x^2检验分析结果显示survivin的表达各TNM分期之间差异有统计学意义（P〈0．05）,分期越晚阳性率越高。MMP-7的表达在患者的年龄、性别、肿瘤部位、肿瘤最大径、肿瘤分化程度、肿瘤大体、组织类型、TNM分期之间差异均无统计学意义（P〉0．05）。Cox单因素及多因素分析结果显示MMP-7阳性、survivin阳性是结肠癌患者肿瘤死亡的独立危险因素。结论：MMP-7、survivin均与结肠癌的发生相关,是影响结肠癌患者肿瘤死亡的独立危险因素。     

Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis

OBJECTIVE: To investigate the expression of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in gastric carcinomas, and to correlate this expression with clinicopathological parameters and angiogenesis. METHODS: Ninety-six resected tumor specimens from patients with gastric carcinoma were obtained, and 30 corresponding paracancerous normal tissues were randomly selected as a control. Immunohistochemical staining was used for detecting the expression of COX-2 and MMP-9. Monoclonal antibody against CD34 was used for displaying vascular endothelial cells, and microvascular density (MVD) was calculated by counting of CD34-positive vascular endothelial cells. RESULTS: The positive expression rates of COX-2, MMP-9 and MVD in the cancerous tissue were 80.2%, 74.0%, and 32.5 +/- 8.3, respectively, which were significantly higher than those in the normal tissue (P < 0.01). COX-2, MMP-9 expression rates and MVD in the patients with stages III and IV were 91.4%, 84.5% and 34.9 +/- 8.7, respectively, which were significantly higher than those in the patients with stages I and II (P < 0.01). In addition, the Spearman rank correlation test showed that tumor MVD was closely associated with COX-2 (r = 0.311, P < 0.01) and MMP-9 (r = 0.349, P < 0.01) expressions. CONCLUSIONS: Overexpression of COX-2 and MMP-9 is related to tumor invasion and lymph node metastasis in the gastric carcinoma. These results provide evidence that COX-2 contribute to gastric cancer development by promoting MMP-9 expression and angiogenesis.     

原发性肝细胞癌组织中CD147和MMP-2的表达

目的 探讨原发性肝细胞癌(HCC)组织中基质金属蛋白酶-2(MMP-2)和细胞黏附因子CD147的表达与临床病理参数之问的关系.方法 应用免疫组织化学Evision法检测47例HCC组织及其癌旁组织中MMP-2和CD147的表达情况.结果 47例HCC组织中MMP-2和CD147的表达阳性率分别为63.8﹪(30/47)和57.5﹪(27/47),明显高于癌旁肝组织中的阳性率(8.5﹪和6.4﹪).MMP-2和CD147在TNM分期Ⅲ-Ⅳ期组中的阳性表达率高于TNM分期Ⅰ-Ⅱ期组(P＜0.01),肿块最大径≥5 cm病例的阳性率明显高于肿块最大径＜5 cm HCC病例的阳性率(P＜0.01),有转移组的阳性率高于无转移组(P＜0.01).本组HCC组织中MMP-2的表达和CD147的表达之间存在正相关(r=0.42,P＜0.01).结论 MMP-2和CD147的表达与HCC的TNM分期、肿块大小和转移密切相关,可作为判断HCC侵袭性的一个指标.     

Prognostic factors and natural history in lymph node-negative breast cancer patients

Summary The prognostic significance of clinical and histological factors as well as hormone receptors was analyzed in a population of 3,064 lymph node-negative breast cancer patients operated in the Stockholm region between 1976 and 1988. None of these patients received systemic adjuvant treatment. Multivariate analysis showed that only histological tumor size, number of examined axillary lymph nodes, and progesterone receptors were independent prognostic factors in terms of recurrence-free interval. An individual risk of recurrence was calculated taking into account these three factors to discriminate between three groups of patients with a risk of less than 15%, 15–25%, and more than 25% of recurrence at 5 years. Similar results were obtained taking into account only the first two factors. The prognostic information added by the knowledge of progesterone receptors only changed the recurrence rate in approximately 3%. This study showed that conventional prognostic factors permit the identification of high risk lymph node-negative breast cancer patients. Results obtained by the use of new more sophisticated factors should be compared with those obtained analyzing strong conventional prognostic factors.     

血管内皮生长因子和基质金属蛋白酶-2在肝细胞肝癌中的表达及临床意义

目的研究血管内皮生长因子（VEGF）和基质金属蛋白酶-2（MMP-2）在肝细胞肝癌（以下简称肝癌）中的表达,及其与肝癌复发转移的关系。方法采用免疫组化方法检测90例肝癌手术切除标本的VEGF及MMP-2的表达情况。结果肝癌组织中VEGF与MMP-2的阳性率分别为76.7％与60.0％。MMP-2与VEGF的表达呈正相关（rs=0．32）,且两者均与复发转移正相关（rs=0.31,rs=0.32）。VEGF（-）组、VEGF（＋）组和VEGF（＋＋）组患者的2年无瘤生存率分别为71.4％、43．5％和30．4％（P〈0．01）;MMP-2（-）组和MMP-2（＋）组的2年无瘤生存率分别为66.7％和32．8％（P〈0.01）。多因素分析显示,肝癌组织中VEGF与MMP-2的表达水平、术前播散结节及镜下癌栓是肝癌复发转移的独立影响因素。结论肝癌组织中VEGF和MMP-2的表达水平结合临床病理特征（术前播散结节及镜下癌栓）,可评价肝癌患者术后复发转移的风险。