骨桥蛋白在大肠癌和大肠癌肝转移灶中的表达及其临床意义

目的：检测骨桥蛋白（osteopontin OPN)mRNA在大肠癌及大肠癌肝转移灶中的表达,并探讨其在大肠癌发生、发展及肝转移中的临床意义。方法：提取44例大肠癌及癌旁正常组织,20例大肠癌肝转移灶及3例正常肝组织RNA,采用RT－PCR半定量法检测其OPN mRNA的表达。并用原位杂交行组织定位检测。结果：44例大肠癌组织OPN表达高于癌旁正常组织（t=4.89,P=0.000)。44例大肠癌组织OPN mRNA表达率为18．2％,而在20例肝转移灶中表达率达80．0％（χ^2=22.42,P=0.000）。原位杂交表明,OPN mRNA定位于大肠癌细胞浆。结论：OPN mRNA在大肠癌组织中表达高于正常组织,而在大肠癌肝转移灶中呈更高表达,提示OPN可能是大肠癌肝转移的预测指标之一。     

Ezrin在胃癌组织中的表达及其临床意义

目的 探讨Ezrin在胃癌发生及发展过程中的作用.方法 收集2008年6月至2009年5月第三军医大学西南医院全军普通外科中心收治的60例胃癌患者的胃癌组织及正常胃黏膜组织标本,分别采用RT-PCR和Western blot法检测标本中Ezrin mRNA及蛋白的表达情况,分析Ezrin与患者性别、年龄、肿瘤分化程度、病理分期、浸润深度及淋巴结转移间的关系.采用t检验、x2检验、Spearman等级相关检验进行统计学分析.结果 60例正常胃黏膜组织中有33例(55％) Ezrin mRNA表达水平升高,45例(75％)Ezrin蛋白表达水平升高;60例胃癌组织中有21例(35％) Ezrin mRNA表达水平升高,22例(37％) Ezrin蛋白表达水平升高.Ezrin mRNA及蛋白在正常胃黏膜组织中的表达水平分别为1.30±0.04和3.57±0.45,在胃癌组织中的表达水平分别为0.53±0.36和0.96±0.18,两者比较,差异有统计学意义(t=5.309,22.617,P＜0.05).胃癌组织中Ezrin mRNA及蛋白表达水平呈正相关(r=0.602,P＜0.05).Ezrin mRNA和蛋白表达在胃癌不同病理分期、不同浸润深度、有无淋巴结转移方面差异有统计学意义(x2=6.41,6.49,4.62;5.40,8.87,4.12,P＜0.05),而在性别、年龄和分化程度方面差异无统计学意义(x2=0.50,0.07,1.07;0.01,1.16,1.96,P＞0.05).结论 胃癌组织中Ezrin表达水平降低,这可能是胃癌的发生、发展及转移的机制之一.     

Clinical significance of osteopontin expression in T1 and T2 tongue cancers

BACKGROUND: Osteopontin (OPN) is considered to be a tumor-related protein associated with tumor aggressiveness and metastasis. METHODS: Immunohistochemistry was used to study the clinical significance of OPN expression in T1 and T2 tongue cancers. RESULTS: Positive OPN expression significantly correlated with higher tumor classification (T) (p = .004), positive nodal classification (N) (p < .001), greater tumor thickness (p < .001), and presence of tumor necrosis (p = .016), respectively. The unfavorable cumulative 5-year disease-free survival rate significantly correlated with positive OPN expression (p < .001), T2 (p = .024), positive N (p < .001), greater tumor thickness (p = .023), and positive tumor necrosis (p = .003). However, taking CD105 into consideration, only CD105 expression was the independent prognostic factor for survival by Cox's regression analysis. CONCLUSION: Overexpression of OPN in the tumors implicated a more aggressive tumor behavior and was an important factor for survival. In addition, there might be relationship between OPN and CD105 expressions in angiogenesis.     

碱性成纤维细胞生长因子和基质金属蛋白酶-9 mRNA表达与胃癌临床病理学及生存期的关系

目的探讨碱性成纤维细胞生长因子(bFGF)和基质金属蛋白酶-9(MMP-9)mRNA在胃癌中的表达及其与肿瘤微血管密度(MVD)、浸润转移和生存期的关系.方法应用原位杂交和免疫组织化学技术,检测105例胃癌组织中bFGF mRNA和MMP-9 mRNA及CD34蛋白的表达.结果bFGF mRNA和MMP-9 mRNA在胃癌中的阳性表达率分别为60.95%和58.1%;阳性表达组的平均血管数(46.09±11.52)个/0.72 mm2和(43.75±13.41)个/0.72 mm2分别显著高于阴性表达组的平均血管数(29.41±12.47)个/0.72 mm2和(33.45±13.92)个/0.72 mm2;bFGF mRNA和MMP-9 mRNA的阳性表达率与肿瘤浸润深度(rs=0.211, P=0.031; rs=0.335, P=0.001)、生长方式(rs=0.324,P=0.001; rs=0.267, P=0.006)、脉管侵犯(rs=0.579, P=0.001; rs=0.209, P=0.032)、淋巴结转移(rs=0.405, P=0.001; rs=0.343, P=0.001)及远处转移(rs=0.474, P=0.001; rs=0.468, P=0.001)有关; MVD分别与bFGF mRNA(t=3.207, P=0.002)和MMP-9 mRNA(t=7.035, P=0.001)的表达水平呈正相关;阳性表达组及MVD值≥39.5的病例的平均生存时间和5年生存率均显著低于阴性表达及MVD值<39.5的病例.结论胃癌组织中bFGF和MMP-9表达与肿瘤微血管密度及生存期密切相关,两者在促进胃癌血管生成方面具有协同作用,因此对估计预后和指导治疗都具有重要意义.     

Increased Osteopontin-Positive Macrophage Expression in Colorectal Cancer Stroma with Synchronous Liver Metastasis

Background  

The macrophages that infiltrate the tumor stroma are termed tumor-associated macrophages (TAMs). TAMs contribute to hematogenous spread of cancer cells especially liver metastasis. Osteopontin (OPN) is also related to tumor metastasis and proliferation of tumors. OPN is mainly expressed in macrophages of stroma other than that of tumor cells. The aim of the present study was to investigate differences in OPN-positive TAMs between cases of colorectal cancer with synchronous liver metastasis and those without liver metastasis.     

食管鳞癌G3BP和骨桥蛋白的表达及其对患者预后的影响

目的研究食管鳞癌组织中GTP酶激活蛋白SH3功能区结合蛋白(G3BP)和骨桥(OPN)蛋白的表达及其与食管鳞癌生物学行为之间的关系。方法采用免疫组织化学方法检测80例食管鳞癌组织中G3BP和OPN蛋白的表达情况,探讨它们与食管鳞癌的肿瘤大小、组织分化程度、TNM分期、淋巴结转移和预后的关系。结果(1)G3BP蛋白在食管鳞癌组织中的阳性表达率为71.3%,它在淋巴结转移组的阳性表达率高于无淋巴结转移组(Z=-2.283,P=0.022);而与肿瘤大小、组织分化程度、TNM分期无关(P>0.05);G3BP蛋白阳性表达组患者的术后生存时间较阴性表达组短,差异有统计学意义(P=0.000)。(2)OPN蛋白在食管鳞癌组织中的阳性表达率为100%,OPN蛋白的表达水平与组织分化程度(X~2=10.766,P=0.005)及淋巴结转移(Z=-2.289,P=0.022)有关,而与肿瘤大小和TNM分期无关(P>0.05);OPN蛋白的表达水平越高,患者术后生存时间越短(P=0.000)。(3)G3BP蛋白和OPN蛋白在食管鳞癌组织中的表达之间存在正相关性(r(?)=0.376,P=0.001)。结论食管鳞癌组织G3BP和OPN蛋白的表达与淋巴结转移情况及患者的预后有密切关系。     

β-微管蛋白的表达对胃癌根治术后辅助化疗的影响及其与预后的关系

目的：探讨胃癌患者胃癌组织中β-微管蛋白表达水平对胃癌根治术后紫杉醇化疗效果的影响。方法：选择接受胃癌根治术并术后进行紫杉醇辅助化疗的332例胃癌患者的组织样本,采用 RT-PCR法检测β-微管蛋白的mRNA表达水平,分析患者临床特征与β-微管蛋白mRNA表达的关系;Kaplan-Meier法比较β-微管蛋白高、低表达组生存时间的差异。结果：β-微管蛋白的mRNA表达水平与患者年龄、性别、肿瘤部位和肿瘤大小均无明显关系（均P>0.05）,而与分化程度、TNM分期、淋巴结转移和远处转移有关（均P<0.05）;β-微管蛋白的mRNA高表达组患者的术后生存时间比低表达组患者术后生存时间短,差异有统计学意义（P<0.05）。结论：胃癌组织中的β-微管蛋白表达水平与胃癌根治术及术后紫杉醇辅助化疗患者的远期生存率有密切关系,可作为患者预后的判断指标。

     

胃良恶性病变组织中VHL和HIF-1α及其mRNA表达与MV计数的关系

目的：研究胃良恶性病变组织中VHL和HIF-1α及其mRNA表达水平和MV计数及其临床病理意义。方法：取49例胃癌,20例癌旁组织,36例淋巴结转移灶和80例不同类型胃良性病变手术切除或胃镜活检标本常规制作石蜡包埋切片,用EnVisionTM免疫组化法检测VHL和HIF-1α表达和MV计数,用原位杂交法检测VHL和HIF-1αmRNA表达。结果：胃癌组织VHL及其mRNA表达阳性率明显低于癌旁组织及各类型胃良性病变（P<0.05或P<0.01）,胃癌组织HIF-1α及其mRNA表达阳性率明显高于癌旁组织及各类型胃良性病变（P<0.05或P<0.01）,胃癌组织MV计数明显高于癌旁组织和各种类型胃良性病变（P<0.01）, VHL及其mRNA阴性表达和（或）HIF-1α及其mRNA阳性表达的癌旁组织及胃良性病变黏膜上皮均呈轻至重度不典型增生;胃癌原发灶与相应淋巴结转移灶比较VHL和HIF-1α及其mRNA表达阳性率及MV计数间,差异无统计学意义（P>0.05）。胃癌组织学分级Ⅱ级、浸润深度T1+T2、无淋巴结转移及无远处转移病例HIF-1α及其mRNA表达阳性率及MV计数明显低于组织学分级Ⅲ+Ⅳ级、浸润深度T3+T4、区域淋巴结转移及远处器官转移者（P<0.05或P<0.01）,但VHL及其mRNA表达阳性率则与HIF-1α相反（P<0.05或P<0.01）;N1站淋巴结转移者VHL及其mRNA表达阳性率明显高于N2+N3站淋巴结转移病例（P<0.05）;VHL和HIF-1α及其mRNA在胃癌组织中表达呈高度不一致性（χVHL=14.66,P<0.01;χ VHLmRNA=6.74,P<0.05）;VHL及其mRNA阳性者或HIF-1α及其mRNA阴性者MV计数明显低于VHL及其mRNA阴性或HIF-1α及其mRNA阳性者（P<0.01）。结论：VHL和HIF-1α及其mRNA表达水平可能是反映胃癌发生、进展、临床生物学行为及预后的重要标记物,VHL和HIF-1α及其mRNA在胃癌组织中表达可能存在负性调节作用;VHL及其mRNA可能抑制胃癌组织中微血管生成,HIF-1α及其mRNA可能促进微血管生成。     

Osteopontin induced by macrophages contribute to metachronous liver metastases in colorectal cancer

Even after radical surgery for stage II and stage III colorectal cancer, metachronous liver metastasis is frequently observed. The aim of this study was to identify the risk of metachronous liver metastasis with retrospective clinicopathological study. Immunohistochemistry was performed to evaluate the expression of Osteopontin (OPN), CD-68, and CD105 in 41 cases of stage II and stage III colorectal cancer tissue. Stage II and stage III colorectal cancer patients who had undergone R0 resection were classified into two groups: with metachronous liver metastasis (m-LM; n = 17) and without liver metastases (control; n = 24). Additionally, double-immunofluorescence staining was performed using antibodies to OPN and CD68. OPN-positive cells were frequently colocalized with CD68 immunoreactivity. OPN and microvascular density expression in the central area were significantly higher in the m-LM (OPN; control 4.3 ± 0.56, m-LV 10.8 ± 1.48, P < 0.05; microvascular density control 18.5 ± 2.86, m-LV 31.4 ± 4.39, P < 0.05), while CD68 expression in the invasive margin was significantly higher in the control group (control 98.9 ± 7.31, m-LV 28.2 ± 3.18, P < 0.05). These results suggest that the risk of metachronous liver metastasis could be well predicted by immunohistochemical staining of OPN in the central areas, and CD68 in the invasive margins of tumors.     

突变型p53与Nampt在胃癌组织中的表达及其与预后的关系

目的：探讨突变型p53（mutp53）和尼克酰胺磷酸核糖转移酶（Nampt）在胃癌组织中的表达及其对患者预后的影响。方法：用免疫组化法检测68例胃癌患者胃癌组织及癌旁正常胃黏膜组织中p53（免疫组化检测到的p53主要为mutp53）与Nampt的表达,分析mutp53与Nampt表达与患者临床病理因素及预后的关系。 结果：胃癌组织中mutp53与Nampt的阳性表达率均明显高于癌旁正常胃黏膜组织（均P<0.05）;mutp53的高表达与肿瘤大小、浸润深度、淋巴结转移及TNM分期有关,而Nampt的高表达与肿瘤浸润深度、淋巴结转移及TNM分期有关（均P<0.05）。胃癌组织中,p53表达与Nampt表达呈明显正相关（r=0.982,P<0.05）。p53阳性表达患者的中位生存期明显短于阴性表达患者,且在p53阳性表达患者中,Nampt同时阳性患者的中位生存期明显短于Nampt阴性患者（均P<0.05）。结论：mutp53与Nampt的表达均与胃癌的恶性生物学行为相关,且两者存在一定的关联性,同时高表达患者预后差。

     

Heparanase protein and gene expression in bladder cancer

PURPOSE: We determined the association of heparanase protein and messenger (m)RNA expression with bladder cancer invasion and metastasis. MATERIALS AND METHODS: The expression of heparanase protein and mRNA was assessed by immunohistochemical staining and in situ hybridization, respectively, in 67 bladder cancer specimens resected at various stages of disease. To our knowledge this is the first systematic study of heparanase protein and mRNA expression in human bladder cancer. RESULTS: The expression of heparanase protein in muscular invasive bladder cancer was significantly higher than in superficial cancer (68% versus 19%, p = 0.0001). It was higher in the primary tumor of patients with lymph node metastatic cancer than those with nonmetastatic cancer (80% versus 37%, p = 0.0006). In high grade disease it was significantly higher than in low grade disease (79% versus 29%, p = 0.0001). The expression of heparanase mRNA was also significantly higher in stage pT3 or greater than in stage pT2 or less bladder cancer (96% versus 33%, p = 0.0003). In metastatic N+ cases it was significantly higher than in nonmetastatic bladder cancer (93% versus 46%, p = 0.0037). The heparanase gene and protein showed similar patterns of expression in bladder cancer. CONCLUSIONS: Our study implies that the expression of heparanase protein and mRNA is associated with bladder cancer invasion and metastasis, and heparanase may have a role in disease progression.     

EphA2与VEGF-C在胃癌中的表达及其与淋巴管生成的关系

目的:探讨胃癌组织中EphA2与VEGF-C的表达及临床意义。方法:用免疫组化法检测82例胃癌组织及其癌旁组织中EphA2与VEGF-C蛋白的表达,以及淋巴管密度(LVD);用real-timePCR检测20例胃癌组织及其癌旁组织中EphA2与VEGF-Cm RNA的表达。分析EphA2与VEGF-C表达与患者临床病理特点及淋巴管生成的关系。结果:EphA2与VEGF-C在胃癌组织中的阳性表达率均明显高于癌旁正常组织(65.8%vs.42.6%;71.9%vs.39.0%,均P0.05)。EphA2与VEGF-C的高表达与肿瘤浸润深度、淋巴结转移、TNM分期有关(均P0.001)。EphA2蛋白与VEGF-C蛋白高表达的胃癌组织中LVD计数分别明显高于两者低表达胃癌组织(15.25±5.41vs.10.95±5.41,P=0.001;14.87±5.71vs.11.00±5.01,P=0.006)。胃癌组织中EphA2与VEGF-C蛋白以及m RNA表达均呈正相关(r=0.375,P=0.001;r=0.559,P=0.01)。结论:EphA2与VEGF-C在胃癌组织中均呈高表达,且可能共同促进淋巴管生成与胃癌淋巴结转移。     

Expression of vascular endothelial growth factor correlates with hematogenous recurrence in gastric carcinoma

BACKGROUND: It has recently been reported that the microvessel density in a tumor correlates with hematogenous metastasis in gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of vascular endothelial growth factor (VEGF), which was thought to be a potent angiogenesis-promoting factor, and hematogenous recurrence in advanced gastric carcinoma. METHODS: The expression of VEGF and the density of the microvessels were examined by immunohistochemistry in patients with advanced gastric carcinoma with serosal invasion who had undergone curative resection. RESULTS: The prognosis of patients with a VEGF-negative tumor was significantly better than that of patients with a VEGF-positive tumor. Multivariate analysis by Cox proportional hazards model showed that the expression of VEGF was an independent prognostic indicator. The expression of VEGF provided a significant estimate of relative risk for the development of hematogenous recurrence by multivariate logistic regression analysis. The microvessel count in VEGF-positive tumors was significantly higher than that in VEGF-negative tumors. CONCLUSIONS: VEGF is associated with hematogenous recurrence. Assessment of the expression of VEGF may therefore prove valuable in identifying patients with gastric carcinoma at high risk for recurrence who would benefit from adjuvant therapy.     

MnSOD expression is increased in metastatic gastric cancer

BACKGROUND: Manganese superoxide dismutase (MnSOD) catalyzes the scavenging of superoxide radicals in order to protect cells from the damage caused by reactive oxygen species. Previous studies implicate MnSOD in cancer progression, but its role in gastric cancer metastasis is poorly understood. MATERIALS AND METHODS: To determine whether MnSOD expression correlates with gastric cancer metastasis, we compared immunostaining for MnSOD in the primary tumors of gastric cancer patients with (n = 15) and without (n = 9) nodal metastases. These patients were matched for risk factors associated with gastric cancer metastasis, such as tumor site, depth, and grade. MnSOD expression was scored positive (increased) if MnSOD staining of tumor cells was more intense than MnSOD staining in corresponding normal gastric epithelial cells. Statistical analyses were via chi(2) test and Fisher's exact test. RESULTS: MnSOD expression was increased in 14 of the 15 (93%) metastatic tumors, compared to only 4 of the 9 (44%) nonmetastatic tumors (P = 0.015). There was no significant difference in staining when the two groups were compared based on tumor grade (P = 0.70) or depth of tumor cell invasion (T stage) (P = 0.22). CONCLUSIONS: MnSOD expression is upregulated in the primary tumors of gastric cancer patients with lymph node metastases. This finding supports an involvement of MnSOD and possibly the reactive oxygen status of the gastric tumor microenvironment in gastric cancer metastasis.