Expression of CD44s mRNA in Gastric Carcinoma

Objective： To study the expression of CD44s mRNA in the occurrence, development and invasion of gastric carcinoma （GC）. Methods： The expressions of CD44s mRNA in 66 cases of GC, 25 cases of superficial gastritis and 25 cases of atypical hyperplasia were examined by in situ hybridization （ISH）. Results： There was no expression of CD44s mRNA in the group of superficial gastritis; the positive rate was 20%（5/25） in the group of atypical hyperplasia and 62.12%（41/66） in the group of gastric carcinoma. The positive rate in poor differentiation group was significantly higher than that in well differentiation group （P〈0.05）, and the positive rate of lymph node metastasis group was significantly higher than that in negative lymph node metastasis group（P〈0.05）. Conclusion： The expression of CD44s mRNA was related to cell differentiation degree and lymph node metastasis, the activation of CD44s gene was related to strong invasion of cancer cells and poor prognosis.     

胃癌组织中Ets-1的表达及其与血管生成临床病理特征和预后的关系

Objective To investigate the expression of Ets-I in gastric carcinoma,pars-cancerous tissue and metastatic lymph nodes,and to determine the relationship between Ets-1 expression and clinicopathological features,angiogenesis and survival of patients with gastric carcinoma.Methods Gastric carcinoma tissue microarray was used to determine Ets-I protein expression by SP immunohistochemical staining in 189 advanced gastric cancer,54 papacancerous tissues,41 metastatic lymph nodes and 32 control tissues.Results The positive rates for Ets-1 expression of the carcinoma,paracancerous and control tissues were 71.4 %,29.6% and 18.8%,respectively,with a significant difference among the three groups(P ＜0.01).In the cancer tissues,the positive rate of Ets-1 protein expression was significantly associated with depth of invasion and lymph node metastasis(P ＜0.01),but not associated with degree of differentiation,Lauren's histological type,sex,age,and size of tumor(P ＞0.05).The positive rates for Ets-1 expression of the 41 gastric cancer and 41 metastatic lymph nodes were significantly different(P ＜0.05).In metastatic lymph nodes,the positive rate for Ets-1 expression was higher.The MVD in Ets-1 positive tumors was higher than that in the Ets-1 negative tumors,with a significant difference(P ＜ 0.05).Kaplan-Meier survival analysis showed that the survival time of Ets-1-negative patients was longer than that of Ets-1-positive patients (P ＜0.05).Cox regression analysis showed that Ets-1 expression was not an independent prognostic factor of gastric carcinoma.Conclusion A higher expression of Ets-1 is involved in carcinogenesis,development,invasion,and metastasis of gastric cancer.Ets-1 plays an important role in angiogenesis in gastric cancer.Ets-1 is a useful marker for predicting the outcome for patients with gastric carcinoma,though it is not an independent prognostic indicator.     

Caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous tissues and chronic non-atrophic gastritis

Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions with the development of gastric cancer.Methods:The expressions of caveolin-1,E-cadherin and β-catenin were detected by biotin-streptavidin-peroxidase(SP) immunohistochemistry on 58 gastric cancer tissues,40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues.The correlation between the expressions of caveolin-1,E-cadherin and β-catenin,and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.Results:The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).Moreover,low expressions of caveolin-1,E-cadherin and β-catenin correlated with tumor size,depth of invasion,lymph node metastasis and TNM stage(P<0.05).The positive rates of caveolin-1 and E-cadherin expressions decreased(P<0.01),while an abnormal rate of β-catenin expression increased inversely,with the degree of atypical hyperplasia(P<0.01).Caveolin-1 expression correlated positively with E-cadherin(r=0.41,P<0.05).Caveolin-1(r= 0.36,P<0.05) and E-cadherin(r= 0.45,P<0.05) expressions negatively correlated with abnormal β-catenin expression.Conclusion: These results suggested that dysregulated expressions of caveolin‐1, E‐cadherin and β‐catenin correlated with the development of gastric cancer and its biological behavior.     

血管内皮生长因子、环氧合酶-2在甲状腺乳头状癌中的表达及其意义

Objective To study the expression and clinical significance of VEGF and COX-2 in papillary thyroid carcinoma (PTC).Methods The expression of VEGF and COX-2 were investigated by immuonhistochemical S-P method in 78 cases of papillary thyroid carcinoma tissue and adjacent tissue.78 cases of PTC including 42 cases with intrathyroidal invasion, 36 cases with extrathyroidal invasion,and 38 cases with lymph node metastasis and 40 cases without lymph node metastasis.Adjacent tissues including 34 cases of nodular goiter(NG),25 cases of Hashimoto thyroiditis(HT)and 19 cases of normal tissue.Results There was a significant difference between thyroid cancer tissue and the tumor free tissue(P＜0.05)and the expression levels of VEGF and COX-2 increased from the tumor free tissue,adjacent tissue to the thyroid cancer tissue(P＜0.05).The expression of VEGF and COX-2 were not related with site of tumor(P＞0.05),but were correlated to the degree of the infiltration and lymph node metastasis in PTC.Expression of COX-2 was correlated positively with VEGF.Conclusion The high expression of VEGF and COX-2 in PTC relates to the development,progression and metastasis of PTC,which may serve as one of the parameters for diagnosis of PTC and determing biological behavior and prognosis of PTC.     

Study on the relationship between P-glycoprotein （P-gp） and C-erbB-2 expression in gastric carcinoma

Objective： To understand the relationship between C-erbB-2 and multidrug resistance （MDR） as well as its clinical significance. Methods： P-gp level was detected by flow cytometry and simultaneously to examine the C-erbB-2 expression level by immunohistochemistry assay in the operating samples. Their relationship was analyzed from 59 cases with gastric carcinoma. Results： The P-gp positive expression was 38/59 （64.4%） cases with gastric carcinoma. The C-erbB-2 positive expression was 21/59 （35.6%） cases with gastric carcinoma. From the analysis of the P-gp and C-erbB-2 relationship, which was involving, range in the gastric carcinoma, that involving two or three sites were more than the site one, in the cases with C-erbB-2 negative. Compared this two groups, there was a significant difference （P = 0.026）. When the C-erbB-2 was positive, the P-gp expression had a significant difference （P = 0.04） in comparing the Ⅲ-Ⅳ stage （lymph node metastasis） with Ⅰ-Ⅱ stage （without lymph node metastasis）. The tumor＇s size, differentiation degree, ages and sex were not related to the C-erbB- 2 and P-gp expression. Conclusion： High level of P-gp expression was related to the C-erbB-2 positive expression in clinical Ⅲ-Ⅳ stage patient with gastric carcinoma （lymph node metastasis）. It suggested that the double positive patient might be a poor prognosis. However, when the C-erbB-2 was negative expression, the clinical staging （with lymph node metastasis） was not related to the P-gp expression in gastric carcinoma patients.     

Relationship between Lymphatic Vessel Density and Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast. METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases. RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma. CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.     

KiSS-1和S100A4在胃癌中的表达变化以及与转移的关系

Objective： To detect the expression of KISS-1 and S100A4 in the primary tumor tissues and lymphatic and visceral metastases and investigate its role in tumorigenesis and metastasis of gastric cancer. Methods： The protein expression of KISS-1 and S100A4 in lymphatic and visceral metastases from advanced gastric cancer specimens was mainly examined by immunohistochemical staining and tissues microarray. Results： Immunohistochemical staining revealed reduced expression of KISS-1 and up-regulated expression of S100A4 in lymph node and visceral metastases. Rates of KISS-1 expression in normal tissues, primary tumor tissues, lymph node and visceral metastases were 95.8%, 74.6%, 60.9% and 57.5%. $100A4 expression in associated cases was 43.6%, 71.8%, 70.3% and 90.0%, respectively. Significant differences in KISS-1 expression was significantly higher in normal tissues than that in primary tumor tissues （P〈0.001）. While significant differences of S100A4 expression could be seen between normal and cancer tissues （P〈0.001） and between visceral and primary tumors （P〈0.05）. Conclusion： Tumor metastasis results from gradual accumulation of abnormal genetic alterations. Down-regulation of KISS-1 and up-regulation of S100A4 play a critical role in metastasis of gastric carcinoma.     

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

Objective： To investigate the expressions of cyclooxygenase （COX）-2 and matrix metalloproteinase （MMP）-9 in cervical carcinoma and their clinical significance. Methods： Immunohistochemistry SP method was used to detect the expressions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix （ICC） and 16 cases of normal cervical epithelium remote from tumor （NCE）. The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results： The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2： 88.9% （64/72）in group ICC and 12.5% （2/16）in group NCE, P = 0.000; MMP-9： 94.4% （68/72） in group ICC and 43.8% （7/16） in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis （r= 0.296, P = 0.012） and stromal invasion （r = 0.257, P = 0.029）. The expression of MMP-9 was positively correlated with FIGO stage （r = 0.329, P = 0.005） and histological grading （r = 0.351, P = 0.003）. The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC （r=0.297, P = 0.011）. Conclusion： The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.     

血管内皮生长因子D在胃癌中表达的意义

 目的 研究血管内皮生长因子D（VEGF-D）在胃癌组织内表达的意义。方法 选择手术后的100例胃癌（区域淋巴结转移阳性和阴性病例各50例），30例正常胃黏膜设为对照组。利用免疫组化EnVision法，检测研究对象胃组织内VEGF-D和VEGF-C的表达。分析VEGF-D阳性表达与临床病理参数和VEGF-C阳性表达的关系。结果 VEGF-C，VEGF-D的阳性染色为棕黄色，主要位于肿瘤细胞的胞质，局灶性或弥散性分布。VEGF-C，VEGF-D阳性表达以（+）或（++）为主；胃癌VEGF-C、VEGF-D阳性表达率分别为51 %和60 %；对照组分别为10 %和20 %（P＜0.05）；VEGF-D阳性高表达（++）与区域淋巴结转移、淋巴管受侵和VEGF-C阳性表达相关，与肿瘤最大径、肿瘤位置、肿瘤浸润深度、肿瘤肉眼分型、肿瘤组织分化、肿瘤血管受侵无关。结论 VEGF-D在胃癌淋巴道转移过程中具有较重要的作用。     

人胃癌VEGF-C、VEGF-D的表达与淋巴结转移的关系

目的 通过从蛋白水平检测VEGF-C、VEGF-D在正常胃黏膜及胃癌中的表达情况,探讨胃癌发生淋巴结转移的机制.方法 应用免疫组化SABC法检测VEGF-C、VEGF-D在正常胃黏膜及胃癌组织中的表达情况.结果 VEGF-C在正常胃黏膜中阴性表达,在胃癌组织中有选择性的表达,阳性率为44.4%,胃癌组与正常胃黏膜组比较差异有统计学意义(P＜0.01).VEGF-D在正常胃黏膜中无表达,在胃癌组织中阳性率为41.3%,胃癌组与正常胃黏膜组比较差异有统计学意义(P＜0.01).在有淋巴结转移组和无淋巴结转移组,VEGF-C的阳性表达率分别为64.5%和25.0%,两组间比较差异有统计学意义(P＜0.05).VEGF-D在这两组中的阳性表达率分别为61.3%和21.9%,两组间比较差异有统计学意义(P＜0.05).且VEGF-C、VEGF-D的阳性表达与胃癌的组织学分级、浸润深度密切相关.结论 VEGF-C、VEGF-D的过表达可能参与了胃癌的淋巴结转移.     

VEGF-C,VEGF-D在乳腺癌中的表达及其与淋巴结转移及预后的关系

目的探讨VEGF-C和VEGF-D在乳腺癌组织中的表达以及与淋巴结转移、预后的相关性。方法采用SP免疫组化法检测78例乳腺癌癌组织和30例癌旁组织中VEGF-C,VEGF-D的表达水平,并完成所有患者的5年的随访资料。结果 78例乳腺癌癌组织中VEGF-C/D表达与癌旁组织相比差异有统计学意义(P<0.05);乳腺癌中VEGF-C表达与VEGF-D表达无相关性。VEGF-C,VEGF-D的表达水平与乳腺癌脉管内侵犯、淋巴结转移密切相关(P<0.05),但与年龄、肿瘤大小、TNM临床分期、ER、PR及Her-2的表达无关(P>0.05)。VEGF-C和VEGF-D的表达水平与乳腺癌的总生存期及无病生存期密切相关(P<0.05)。结论 VEGF-C,VEGF-D在乳腺癌组织中呈高表达;VEGF-C/D的表达水平与乳腺癌淋巴结转移能力和预后密切相关。     

胆囊癌组织中血管内皮生长因子C和D的表达及其与淋巴管和血管生成的关系

目的 探讨胆囊癌组织中血管内皮生长因子C(VEGF-C)和VEGF-D的表达及其与淋巴管和血管生成的关系.方法 采用免疫组化法检测50例胆囊癌组织中VEGF-C、VEGF-D、D2-40和CD31的表达,以10例癌旁正常胆囊组织和19例慢性胆囊炎作为对照,并分析其与临床病理诸因素的关系.结果 50例胆囊癌组织中,32例VEGF-C表达阳性,阳性率为64.0%,31例VEGF-D表达阳性,阳性率为62.0%,均高于癌旁正常组织(P<0.05),但与慢性胆囊炎差异无统计学意义(P>0.05).VEGF-C的表达与胆囊癌患者的年龄和淋巴结转移有关,VEGF-D的表达仅与胆囊癌患者的淋巴结转移有关.50例胆囊癌组织的微淋巴管密度(MLVD)和微血管密度(MVD)分别为6.94±3.6和36.1±12.8.VEGF-C阳性组和VEGF-D阳性组的MLVD和MVD均高于阴性组.MLVD与淋巴结转移有关,MVD与淋巴结转移、分化程度有关.VEGF-C与VEGF-D的表达呈正相关(r=0.498,P<0.01).结论 在胆囊癌中,VEGF-C和VEGF-D参与胆囊癌的淋巴生成和血管生成的调节,通过增加瘤周淋巴管的密度促进肿瘤细胞的淋巴结转移.     

VEGF-C and VEGF-D Expression and its Correlation with Lymph Node Metastasis in Esophageal Squamous Cell Cancer Tissue

Background: To explore vascular endothelial growth factor C (VEGF-C) and VEGF-D expression andits correlation with lymph node metastasis in esophageal squamous cell cancer (ESCC) tissue. Materials andMethods: Immunohistochemical methods were applied to detect the levels of VEGF-C and VEGF-D expressionin 64 surgicall removal ESCC tissues, tissues adjacent to cancer and normal tissues, and the relationship betweenVEGF-C and VEGF-D expression and lymph node metastasis was analyzed. Results: Both VEGF-C and VEGF-Dwere expressed by varying degrees in esophageal cancer tissue, the tissue adjacent to cancer and normal tissue,and the positive expression rate went down successively. The positive expression rates of VEGF-C (59.4%) andVEGF-D (43.8%) in esophageal cancer tissue were significantly higher than in the tissue adjacent to cancer(34.4%, 15.6%) and normal tissue (20.3%, 12.5%), respectively, in which significant differences were manifested(p<0.01). Positive expression rates of VEGF-C and VEGF-D in esophageal cancers with lymph node metastasiswere markedly higher than without such metastasis (p<0.01), while those in the tissue with TNM staging I~IIwere markedly lower than that with TNM staging III~IV (p<0.01). Conclusions: Both VEGF-C and VEGF-Dare highly expressed in ESCC tissue, which may be related to the lymph node metastasis of cancer cells. Hence,VEGF-C and VEGF-D can be clinically considered as important reference indexes of lymph node metastasis inesophageal cancer.     

VEGF-C和VEGF-D在胰腺癌淋巴转移中的意义

目的 分析胰腺癌肿瘤中心和肿瘤周边组织中血管内皮生长因子(VEGF)-C、VEGF-D与微血管密度(MVD)、微淋巴管密度(MLVD)的关系,探讨VEGF-C、VEGF-D在胰腺癌淋巴结转移及发展中的意义.方法 免疫组织化学法检测30例胰腺癌组织中VEGF-C、VEGF-D、VEGF受体(VEGFR)-3、CDM蛋白的表达情况.结果 30例胰腺癌中肿瘤周边部位VEGF-C、VEGF-D蛋白阳性率分别为73.3%和56.7%,显著高于肿瘤中心部位(30.0%和16.7%,P<0.01).VEGF-C、VEGF-D高表达的肿瘤周边部位淋巴结转移、淋巴管和血管浸润显著增加(P<0.01).VEGF-C蛋白阳性组MVD高于阴性组,MLVD显著高于阴性组(P<0.01),淋巴结转移增多;VEGF-D蛋白阳性组与阴性组相比MVD无变化(P=0.07),MLVD高于阴性组(P<0.01),淋巴结转移增加.结论 胰腺癌中肿瘤周边区域中VEGF-C、VEGF-D的表达与患者淋巴结转移显著相关,并介导其淋巴管生成;而VEGF-C可能主要参与胰腺癌的血管生成和淋巴管生成的调节,VEGF-D可能仅参与其淋巴管生成的调节.     

VEGF-C和VEGF-D在胃癌及相关淋巴结组织中表达和临床意义的研究

目的：比较血管内皮生长因子C（vascular endothelial growth factor C,VEGF-C）和血管内皮生长因子D（vascular endothelial growth factor D,VEGF-D）在胃癌和相关淋巴结的表达,并评价其预后意义.方法：采用原位杂交技术检测45例胃癌患者原发病灶和转移淋巴结中VEGF-C和VEGF-D mRNA的表达水平;并检测转移及非转移淋巴结中VEGF-C和VEGF-D mRNA表达差异.结果：71%和62.2%的胃癌原发病灶可见VEGF-C和VEGF-D mRNA表达,原发病灶阳性者,相应的淋巴结转移病灶都可见VEGF-C和VEGF-D mRNA表达,55.6%和51.1%的胃癌患者淋巴结转移病灶VEGF-C和VEGF-D mRNA表达水平高于原发病灶,原发病灶和转移病灶淋巴管生成表达水平的差异与胃癌的预后密切相关（P＜0.05）.结论：胃癌癌细胞转移至淋巴结后淋巴管生成因子表达可能进一步提高,以进一步增强转移能力.     

Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes

The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes.     

Expression of vascular endothelial growth factor C and D (VEGF-C and -D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma

BACKGROUND: Vascular endothelial growth factor C (VEGF-C) and D (VEGF-D) are considered to be potentially lymphangiogenic and can selectively induce hyperplasia of the lymphatic vasculature. In this study, we aimed to clarify the relation between expression of VEGF-C and -D and lymphatic metastasis in early gastric cancers. METHODS: Using the specific antibodies, we classified 105 cases which were treated as gastrectomy with standard lymphadenectomy at the First Department of Surgery, Tokyo University Hospital, between 1994 and 2001, into three groups (diffuse type, focal type and negative type) for VEGF-C and two groups (positive and negative) for VEGF-D. RESULTS: There was a significant correlation between the expression of VEGF-C and -D and lymphatic invasion but not with venous invasion. All of the 22 cases that were negative for VEGF-C and -D were histologically classified as adenocarcinoma of undifferentiated type and showed negative lymph node metastasis and also negative lymphatic invasion. VEGF-C was positive in all tumors of differentiated type, while its expression varied in tumors of undifferentiated type. The VEGF-D positive rate is much lower than that of VEGF-C. In undifferentiated tumors in particular, VEGF-D was positive only in 4/64 (6%) and three of these four had nodal metastasis. Therefore, in tumors of differentiated type, expression of VEGF-C and -D had no clinical relevance. In tumors of undifferentiated type, the negative expression of VEGF-C suggests lack of nodal metastasis, while the positive expression of VEGF-D suggests nodal metastasis. The lymph node metastasis was significantly related to the expression of VEGF-C and -D in adenocarcinomas of undifferentiated type but not in those of differentiated tumors. CONCLUSIONS: In early gastric cancers of histologically undifferentiated type with negative expression of VEGF-C and -D, limited surgery might be safely applied because the possibility of nodal metastasis is very low. These observations are based only on retrospective analysis of a small case series and further evaluation with a larger number of cases is necessary.