Coordinate Regulation of Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 Expression in Human Vascular Smooth Muscle Cells

The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by human vascular smooth muscle cells (SMC) was monitored as a function of the phenotypic modulation in vitro. Cell phenotype was manipulated by varying serum concentration and cell density. Synthetic phenotype was characterized by a minimum expression of the contractile proteins and a maximal proliferation rate. Contractile phenotype was quiescent and expressed a maximal level of contractile proteins. Synthetic cells expressed the highest levels of both MMP-1 and TIMP-1 and displayed maximal collagenolytic activity. No significant change was detected in MMP-2 expression or catalytic activity. Enzyme immunoassays revealed that MMP-1 expression fell by 77 ± 2.4-95 ± 0.5%, and that of TIMP-1 by 34 ± 0.5-59 ± 1.9%, as the cells acquired a contractile phenotype. The level of the MMP-1/TIMP-1 complex was similarly reduced by 78 ± 2.9-85 ± 1.6%. These data demonstrate that the expression of MMP-1 and TIMP-1 are coordinately regulated with SMC phenotype.     

An Absence of Stromal Caveolin-1 Expression Predicts Early Tumor Recurrence and Poor Clinical Outcome in Human Breast Cancers

Previously, we showed that caveolin-1 (Cav-1) expression is down-regulated in human breast cancer-associated fibroblasts. However, it remains unknown whether loss of Cav-1 occurs in the breast tumor stroma in vivo. Here, we immunostained a well-annotated breast cancer tissue microarray with antibodies against Cav-1 and scored its stromal expression. An absence of stromal Cav-1 was associated with early disease recurrence, advanced tumor stage, and lymph node metastasis, resulting in a 3.6-fold reduction in progression-free survival. When tamoxifen-treated patients were selected, an absence of stromal Cav-1 was a strong predictor of poor clinical outcome, suggestive of tamoxifen resistance. Interestingly, in lymph node-positive patients, an absence of stromal Cav-1 predicted an 11.5-fold reduction in 5-year progression-free survival. Clinical outcomes among patients positive for HER2, and patients triple-negative for estrogen receptor, progesterone receptor and HER2, were also strictly dependent on stromal Cav-1 levels. When our results were adjusted for tumor and nodal staging, an absence of stromal Cav-1 remained an independent predictor of poor outcome. Thus, stromal Cav-1 expression can be used to stratify human breast cancer patients into low-risk and high-risk groups, and to predict their risk of early disease recurrence at diagnosis. Based on related mechanistic studies, we suggest that breast cancer patients lacking stromal Cav-1 might benefit from anti-angiogenic therapy in addition to standard regimens. We conclude that Cav-1 functions as a tumor suppressor in the stromal microenvironment.Carcinoma cells grow in a complex tumor microenvironment composed of (i) non-epithelial cells (including fibroblasts, pericytes, endothelial, and inflammatory cells), (ii) extracellular matrix, and (iii) secreted diffusible growth factors/cytokines.^1,2,3 Although under normal physiological conditions the stroma serves as an important barrier to malignant transformation, its role changes during neoplastic transformation. Instead, the stroma plays a key role in driving cancer cell invasiveness and progression.⁴ Recently, it was demonstrated that fibroblasts isolated from tumor stroma can promote tumor growth.^1,2,3,5 This population of tissue fibroblasts termed “cancer associated fibroblasts” (CAFs) is characterized by a hyperproliferative phenotype, and these cells secrete increased amounts of growth factors, extracellular matrix components, and matrix metalloproteinases.^5,6 CAFs also show an ability to prevent cancer cell apoptosis, induce cancer cell proliferation, and stimulate tumor angiogenesis.⁷ In vitro studies of breast carcinomas showed that CAFs mixed with epithelial carcinoma cells are more proficient than normal fibroblasts at enhancing tumor growth and give rise to highly vascularized tumors.⁸ To date, the mechanisms that govern the conversion of benign mammary stromal fibroblasts to tumor-associated fibroblasts are poorly understood, and their relationship to disease outcome has not been addressed.Down-regulation of caveolin-1 (Cav-1) is one of the mechanisms implicated in the oncogenic transformation of fibroblasts. Caveolins are the principal protein component of caveolae, which are located at the cell surface in most cell types.⁹ One of the caveolins, Cav-1, plays a major role in tumorigenesis through its various functions such as lipid transport, membrane trafficking, gene regulation, and signal transduction.¹⁰ In cell culture, the transformation of NIH-3T3 fibroblasts with various activated oncogenes, such as H-Ras (G12V), Bcr-Abl, or v-Abl, causes dramatic reductions in Cav-1 protein expression.^11,12Furthermore, knock-down of endogenous Cav-1 in NIH-3T3 fibroblasts promotes anchorage-independent growth in soft agar and tumor formation in nude mice, which could be reversed by Cav-1 re-expression.¹³ Finally, Cav-1^−/− null fibroblasts have a hyperproliferative phenotype (similar to CAFs) and Cav-1 re-expression drives their arrest in the G0/G1 phase of the cell cycle.¹⁴ Taken together, these data suggest that loss of Cav-1 leads to the oncogenic transformation of fibroblasts, where Cav-1 normally functions as a transformation suppressor that prevents cell cycle progression.Using primary cell cultures established from surgically excised breast tumors, we recently demonstrated that Cav-1 is down-regulated in human breast CAFs when compared with matching normal fibroblasts isolated from the same patient.¹⁵ In addition, orthotopic transplantation of Cav-1^+/+ tumor tissue into the mammary stroma of Cav-1^−/− null mice results in up to a ∼twofold increase in tumor mass, functionally demonstrating that the mammary stroma of Cav-1^−/− mice behaves as a tumor promoter.¹⁶ However, to date, there is no study addressing the clinical significance of stromal Cav-1 expression in invasive carcinoma of the breast in vivo.The aim of this study was to evaluate the in vivo stromal expression of Cav-1 in a large series of invasive breast carcinomas and to examine the association between stromal Cav-1 expression, clinicopathological variables, and patient outcome. Our results indicate that loss of stromal caveolin-1 is a novel breast cancer biomarker that predicts early disease recurrence, metastasis, survival, and tamoxifen-resistance. Clinical outcome in HER2(+) and triple-negative (estrogen receptor [ER]−/progesterone receptor [PR]−/HER2−) patients was also strictly dependent on stromal Cav-1 levels. Remarkably, in lymph node-positive [LN(+)] patients, an absence of stromal Cav-1 was associated with an ∼11.5-fold reduction in 5-year progression-free survival. As such, Cav-1 may function as a critical tumor/metastasis suppressor in the mammary stromal compartment.     

牙周炎牙龈组织MMP-2、TIMP-1的免疫组化研究

目的　探讨来源于宿主的基质金属蛋白酶MMPs及其抑制因子在牙周炎发病中的作用机制。方法　本研究利用免疫组化方法检测 15例牙周炎患者牙龈组织中和 4例健康牙龈中基质金属蛋白酶 2(MMP 2 )、组织抑制因子 1(TIMP 1)的蛋白表达。结果　 15例成人牙周炎组牙龈组织中MMP 2在上皮内及上皮下的炎性组织中均有阳性表达 ,而且阳性率明显高于正常牙龈 (P <0 .0 5 ) ;TIMP 1在牙周炎以及正常的牙龈组织中表达无明显差异。结论　本研究提示基质金属蛋白酶MMP 2参与牙周组织破坏过程 ,参与牙周炎的病理生理机制     

糖尿病大鼠肾组织中NF-κB和MMP-9及TIMP-1表达关系的研究

目的 :研究糖尿病大鼠肾组织中核因子 κB(NF κB)和基质金属蛋白酶 9(MMP 9)及组织基质蛋白酶抑制因子 1(TIMP 1)表达之间的关系方法 :将 3 0只雄性Wistar大鼠随机分为正常对照组 (C组 )、糖尿病未治疗组 (D组 )和糖尿病苯那普利治疗组 (B组 ) ,每组10只 ,利用链脲佐菌素 (STZ)诱导糖尿病模型 ,应用免疫组化方法研究大鼠肾组织中NF κB、MMP 9和TIMP 1的表达 ,并利用HPIAS 10 0 0型医学彩色图像分析系统进行图像分析。结果 :各组间的差异均有显著性意义 (P <0 .0 1)。NF κB与MMP 9成明显负相关 (r =-0 .882 67,P <0 .0 1) ,NF κB与TIMP 1无明显相关 (r =0 .5 2 981,P >0 .0 5 ) ,NF κB与MMP 9/TIMP 1的比值亦成明显负相关 (r =-0 .8685 0 ,P <0 .0 1)。结论 :NF κB对糖尿病大鼠肾组织中MMP 9的表达起重要作用 ,可能参与了糖尿病肾病的发生和发展     

HIF1A Overexpression Is Associated with Poor Prognosis in a Cohort of 731 Colorectal Cancers

Tissue hypoxia commonly occurs in tumors. Hypoxia- inducible factor (HIF)-1 and HIF-2, which are essential mediators of cellular response to hypoxia, regulate gene expression for tumor angiogenesis, glucose metabolism, and resistance to oxidative stress. Their key regulatory subunits, HIF1A (HIF-1α) and endothelial PAS domain protein 1 (EPAS1; HIF-2α), are overexpressed and associated with patient prognosis in a variety of cancers. However, prognostic or molecular features of colon cancer with HIF expression remain uncertain. Among 731 colorectal cancers in two prospective cohort studies, 142 (19%) tumors showed HIF1A overexpression, and 322 (46%) showed EPAS1 overexpression by immunohistochemistry. HIF1A overexpression was significantly associated with higher colorectal cancer-specific mortality in Kaplan-Meier analysis (log-rank test, P < 0.0001), univariate Cox regression (hazard ratio = 1.84; 95% confidence interval, 1.37 to 2.47; P < 0.0001) and multivariate analysis (adjusted hazard ratio = 1.72; 95% confidence interval, 1.26 to 2.36; P = 0.0007) that adjusted for clinical and tumoral features, including microsatellite instability, TP53 (p53), PTGS2 (cyclooxygenase-2), CpG island methylator phenotype, and KRAS, BRAF, PIK3CA, and LINE-1 methylation. In contrast, EPAS1 expression was not significantly associated with patient survival. In addition, HIF1A expression was independently associated with PTGS2 expression (P = 0.0035), CpG island methylator phenotype-high (P = 0.013), and LINE-1 hypomethylation (P = 0.017). EPAS1 expression was inversely associated with high tumor grade (P = 0.0017) and obesity (body mass index ≥ 30 kg/m²) (P = 0.039). In conclusion, HIF1A expression is independently associated with poor prognosis in colorectal cancer, suggesting HIF1A as a biomarker with potentially important therapeutic implications.Tissue hypoxia commonly occurs in tumor, and adaptation to tissue hypoxia appears to be one of important characteristics of malignant cells.^1,2 Hypoxia-inducible factor (HIF)-1 and HIF-2 play a key role in cellular adaptation to hypoxia and regulate the expression of genes responsible for glucose metabolism, angiogenesis, and cell survival.^1,2,3 Thus, HIF and related pathways are potential therapeutic targets.^4,5 Cellular HIF levels are regulated not only by the oxygen-dependent pathway (eg, VHL and prolyl hydroxylase, EGLN) but also by the oxygen-independent pathway (eg, glycogen synthase kinase 3, the phosphatidylinositol 3-kinase pathway, the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway).^6,7 HIF and hypoxia signaling influence a wide variety of pathways including those related to vascular endothelial growth factor (VEGF), cyclins, and MTOR.^1,2 Thus, cellular HIF levels may modify responsiveness to drugs targeting those pathways or hypoxia signaling, and it is of particular interest to examine HIF expression in human cancers. Key regulatory subunits of HIF, HIF1A (the official symbol for HIF-1α), and endothelial PAS domain protein 1 (EPAS1; the official symbol for HIF-2α) are differentially overexpressed^8,9 and have distinct functions in human cancers.^9,10,11 HIF1A expression leads to increased tumor growth and metastasis in some studies,^12,13,14,15 whereas HIF1A inhibits tumor growth by cell cycle arrest or apoptosis induction in other studies.^16,17,18,19 Similar paradoxical effects of EPAS1 have also been reported; EPAS1 appears to promote cancer development and progression in neuroblastoma and renal carcinoma,^20,21,22 whereas it appears to inhibit tumor growth in other cancers including colon cancer.^23,24,25Previous data on HIF1A, EPAS1, and clinical outcome in colorectal cancer have been inconclusive. A study of 90 rectal cancer patients showed poor prognosis associated with HIF1A but not with EPAS1.²⁶ In contrast, another study of 87 colorectal cancer patients reported poor prognosis associated with EPAS1 but not with HIF1A.²⁷ Among studies assessing only HIF1A, some reported its independent prognostic effect^28,29 whereas others did not.^30,31 However, all previous studies^{26,27,28,29,30,31} were limited by small sample sizes (N <136). Considering the increasing importance of the HIF pathway as a potential target for cancer treatment,^1,2,6 the assessment of HIF1A and EPAS1 expression and clinical outcome using a large number of colorectal cancers is needed.We therefore examined prognostic effects of HIF1A and EPAS1 expression among 731 colorectal cancer patients identified in two prospective cohort studies. Moreover, because we concurrently assessed other important molecular events including mutations in KRAS, BRAF, and PIK3CA, LINE-1 hypomethylation, microsatellite instability (MSI), and the CpG island methylator phenotype (CIMP), we could evaluate the effect of HIF1A or EPAS1 expression after controlling for these potential confounders.     

苯那普利对糖尿病大鼠肾组织中MMP-2和TIMP-2表达的影响

目的研究苯那普利对糖尿病大鼠肾组织中基质金属蛋白酶 -2(MMP_2)和组织金属蛋白酶抑制因子_2(TIMP_2)表达的影响。方法将30只雄性Wistar大鼠随机分成3组 :正常对照组 (C组 ,n=10)、糖尿病未治疗组 (DM组 ,n=10)和糖尿病苯那普利治疗组 (DB组 ,n=10)。应用链脲佐菌素(STZ)诱导糖尿病模型。造模成功后 ,用苯那普利对DB组进行治疗性灌胃 ,其余2组均用等量自来水灌胃。4周后 ,将所有大鼠一次性处死 ,摘除肾脏 ,用免疫组化方法 (SP法 )研究MMP_2和TIMP_2的表达 ,应用HPIAS -1000型医学彩色图像分析系统对结果进行图像分析 ,应用SAS8.1统计软件进行医学统计和相关分析。结果采用平均吸光度 (OD值 )作为记录结果 ,MMP_2在C组、DM组和DB组中的OD值分别为 :0.08362±0.00762、0.16372±0.01835和0.13316±0.01357,其中DM组较C组上调约95.8 %,DB组较C组上调约59.2 %,较DM组下调约36.6 % ;TIMP_2在3组中的OD值依次为 :0.07368±0.00638、0.15673±0.02321和0.12142±0.01036,其中DM组较C组上调112.7 % ,DB组较C组上调64.8% ,较DM组下调47.9 % ;而MMP -2/TIMP -2的比值在3组中依次为 :1.135±0.112、1.045±0.131和1.097±0.125,其中DM组较C组下降7.9% ,DB组较C组下降3.3% ,较DM组上升4.6 %。以上各组间差异均具有     

Matrix Metalloproteinases 2, 7, 9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in the Sera of Patients with Bone Tumors

Comparative enzyme immunoassay of matrix metalloproteinases (MMP-2, -7, -9) and their tissue inhibitor-1 (TIMP-1) in the sera of 26 healthy individuals and 54 patients with primary osteal tumors before therapy revealed elevated TIMP-1 levels in the patients with classical central and periosteal osteosarcomas in comparison with the control. In patients, the level of MMP-9 signifi cantly decreased compared to that in healthy individuals, while the levels of MMP-2 and MMP-7 remained unchanged. No differences in serum levels of MMP and TIMP-1 associated with gender, age, primary osteal tumor location and size were detected. Overall 3-year survival of patients with classical central osteosarcoma with serum level of MMP-9 below its median was higher than that of patients with MMP-9 level equal to above the median (90.9±8.7 and 50.8±23%, respectively).     

Novel Implications in the Development of Endometriosis: Biphasic Effect of Macrophage Activation on Peritoneal Tissue Expression of Tissue Inhibitor of Metalloproteinase-1

PROBLEM: Elevated levels of activated macrophages are associated with endometriosis, but their role in the etiology of the disease is uncertain. The current study was undertaken to examine whether activated macrophages could modulate peritoneal tissue expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1), which may play a role in the development of endometriosis. METHOD OF STUDY: Female mice were treated with the macrophage activator lipopolysaccharide (LPS), and peritoneum TIMP-1 mRNA was examined by Northern blot analysis. RESULTS: LPS induced a dose-dependent increase (P < 0.05) in TIMP-1 mRNA expression at levels of 1 μg (70.0% ± 5.8% greater than the control), 10 μg (83.0% ± 12.0% greater than the control), and 25 μg (100.0% ± 10.0% greater than the control). In contrast, the administration of 50 μg of LPS resulted in a decrease in TIMP-1 mRNA expression below baseline levels (18.0% ± 6.0% less than the control values). CONCLUSIONS: Activated macrophages and/or their products modulate peritoneum TIMP-1 expression. These data suggest that, in addition to their phagocytotic role in the peritoneal cavity, these immune cells also may play a novel role in influencing the ability of the peritoneum to regulate tissue/cell invasion and in the development of endometriosis through TIMP-1 expression.     

Matrix Metalloproteinase-9 and Tissue Inhibitors of Matrix Metalloproteinase-1 in Plasma of Patients Co-Infected with HCV and HIV

Abstract

Background: Accelerated progression of hepatic fibrosis has been shown in patients co-infected with hepatitis C virus (HCV) and HIV. Liver fibrosis is a dynamic process in which the altered balance between matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) may play a major role. Method: The involvement of MMP-9 and TIMP-1 in HCV liver disease progression in patients co-infected with HIV was evaluated. Plasma concentrations of human MMP-9 and TIMP-1 were assessed in 76 HIV-infected patients; 27 were co-infected with HCV and 49 were HCV negative. 18 healthy donors were included as controls. Results: Patients with HIV infection exhibited a striking increase in TIMP-1 levels; this is more evident in patients with advanced CD4 depletion. There was no elevation in the plasma concentrations of the MMP-9. The highest levels of TIMP-1 were found in the HIV/HCV co-infected patients. The values of TIMP-1 in HIV-infected patients with chronic HCV hepatitis were significantly higher than in HIV-positive individuals without HCV infection, even including those with low CD4 count. No significant differences were seen in the MMP-9 levels. Conclusion: These findings suggest that the altered balance between circulating MMP-9 and TIMP-1 during HIV infection may play an important role in exacerbating liver fibrosis progression in patients co-infected with HCV.     

The Metastasis-Associated Anterior Gradient 2 Protein Is Correlated with Poor Survival of Breast Cancer Patients

The secreted metastasis-inducing protein, human anterior gradient 2 (AGR2), has been independently reported to be associated with either a reduced or an increased survival of different groups of patients with breast cancer. We now aim to analyze the expression of AGR2 in a third completely independent group of patients using a specific AGR2 monoclonal antibody (mAb). Primary tumors from a group of 315 patients suffering from operable (stage I and II) breast cancer with 20-years follow-up were immunocytochemically stained with a specific mAb to AGR2 and associations with prognostic factors and patient survival were analyzed. The mAb specifically recognized AGR2 in Western blots, and positive staining for AGR2 was significantly associated with involved lymph nodes and staining for estrogen receptor α, progesterone receptor, and the metastasis-inducing proteins osteopontin, S100P, and S100A4. After 20 years of follow-up, only 26% of patients with AGR2-positive carcinomas survived compared with 96% of those with AGR2 negative carcinomas, with the highly significant difference in median survival times of 68 and >216 months, respectively (P < 0.0001). Cox’s multivariate regression analysis showed that staining for AGR2 was one of the most significant independent prognostic indicators, with a corrected relative risk of 9.4. The presence of AGR2 in the primary tumor is therefore a possible prognostic indicator of poor patient outcome in breast cancer.Anterior gradient 2 (AGR2) protein is a secreted protein first described in Xenopus laevis embryos, where it induces the formation of the forebrain and the mucus-secreting cement gland.¹ Human AGR2 is also found co-expressed with estrogen receptor α (ERα) in breast cancer cell lines² and its presence significantly correlates with ERα in breast carcinoma specimens.³ Subsequent studies have found elevated expression of AGR2 in adenocarcinomas of the esophagus, pancreas, prostate, and non-small cell lung cancer, showing that it is a widely overexpressed protein in human carcinomas.^{4,5,6,7,8,9,10} We have shown that human AGR2 is expressed at higher levels in malignant, rather than in benign breast tumors,¹¹ and that, when introduced in an expression vector into the benign, nonmetastatic rat mammary cell line, Rama 37,¹² it causes metastasis in syngeneic rats.¹¹ These results suggest that AGR2’s metastasis-inducing properties may contribute toward the malignant progression of some breast cancers. Certain molecules shown to induce metastasis in experimental breast cancer in rodents, for example, S100A4, S100P, and osteopontin (OPN),^13,14,15,16 provide a potential source for markers that may be useful as prognostic factors in predicting patient outcome in human breast cancer.Using a polyclonal antibody (PAb) to AGR2, a strong positive association was shown between AGR2 and ERα and between AGR2 and low histological grade in a retrospective cohort of 351 breast cancer patients treated by adjuvant hormonal therapy.¹⁷ In these patients, levels of AGR2 were also associated with a relatively poor outcome in patients with ERα-positive breast cancers after treatment with antiestrogen therapy.¹⁷ In contrast to these results, it has been reported that in another panel of 155 breast carcinoma patients treated with various adjuvant therapies, immunocytochemically detected AGR2 in the cancer cells was associated with significantly longer patient survival times, although there was still a significant correlation with the presence of ERα and lower tumor grade.¹⁸ To resolve these apparent conflicting associations of AGR2 protein with patient survival, the expression of immunocytochemically detectable AGR2 protein has now been determined in the primary tumors of an independent group of 315 patients suffering from operable breast cancer and treated by surgery alone with no accompanying adjuvant therapy. A new specific monoclonal antibody (mAb) to AGR2, which does not cross-react with the closely-related AGR3 protein,³ has been used to improve the accuracy of detection of AGR2. The results show that, in this large group of breast cancer patients, the presence of immunocytochemically detectable AGR2 protein in the primary tumor is strongly associated with a reduced survival of the corresponding patients.     

Elevated Plasma Matrix Metalloproteinase-9 and Its Correlations with Severity of Disease in Patients with Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) increases patient mortality and medical expenditure, and a real-time and reliable method for the rapid diagnosis of VAP may help reduce fatal complications. Matrix metalloproteinases-9 (MMP-9) is considered significant in the pathogenesis of lung inflammation and infection. Therefore, we examined its relationship with the clinical course of VAP. This retrospective observational study recruited 30 healthy volunteers, 12 patients who used mechanical ventilation without the development of VAP (hereafter, patients without VAP), and 30 patients with a clinical diagnosis of VAP (hereafter, patients with VAP). The activity and level of plasma MMP-9 were determined through a gelatin zymography assay and ELISA. Our results report that both plasma MMP-9 activity and concentration were significantly elevated in the acute stage of patients with VAP when compared with control group and patients without VAP (p < 0.001). Subsequently, the plasma MMP-9 of patients with VAP decreased significantly after antibiotic treatment. Furthermore, plasma MMP-9 concentration was positively correlated with the clinical pulmonary infection score (r = 0.409, p = 0.007), WBCs (r = 0.620, p < 0.001), and neutrophils counts (r = 0.335, p = 0.035). In addition, plasma MMP-9 is an excellent tool for recognizing VAP when the cutoff level is set to 92.62 ng/mL (AUC = 0.863, 95% CI = 0.761 to 0.932). In conclusions, we concluded that MMP-9 levels play a role in the development of VAP and might have the potential to be applied in the development of VAP therapies.     

乳腺肿瘤组织生长抑素受体检测及其临床意义

探讨乳腺良、恶性肿瘤SSR表达的差异对乳腺肿瘤良、恶性的鉴别诊断的价值, 观察SSR表达与ER、PR表达的相关性, 预测乳腺肿瘤生长抑素受体显像的临床价值. 将手术切下的标本分成4组: 乳腺肿瘤恶性组(恶性组)及其对照组(癌旁组), 乳腺肿瘤良性组(良性组)及其对照组(瘤旁组).采用RBA法测定各组织的SSR表达, 采用免疫LsAB法测定ER、PR表达.结果:(1)恶性组、癌旁组、良性组、瘤旁组SSR表达分别为108.6±67.3fmol/mg pr、37.2±9.6fmol/mg pr、43.4±12.6fmol/mg pr、33.9±10.2fmol/mg pr, 恶性组比其对照组及良性组都高, 差异有显著性(P值分别为＜0.001、＜0.01),而良性组与其对照组则无显著性差异(P＞0.05);(2)SSR与ER、PR表达的相关系数分别为0.859、0.750.因此, 大多数乳腺癌组织表达高密度的SSR,可用SSR显像来做良、恶性肿瘤的初步鉴别, SSR表达与ER、PR表达有良好的相关性, 可预测肿瘤恶性程度及其患者预后.