Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion

AIM： To investigate the relation of expression transformation of claudin-1 with invasiveness and metastasis of gastric carcinoma. METHODS： By using immunohistochemistry, expression of claudin-1 in mucosa and invasive front of 136 gastric adenocarcinoma cases and proliferative index （Ki-67） were detected and analyzed. RESULTS： In mucosa, the claudin-1 over-expression rate of mucinous adenocarcinomas （including signetring cell carcinomas） was the highest. It was negatively related with the differentiation but positively related with the invasiveness and metastasis of gastric cancer. In invasive front, the claudin-1 over-expression rate was positively related with the differentiation, invasiveness and metastasis of gastric carcinoma. The expression transformation of claudin-1 was found in gastric carcinoma. The expression of claudin-1 in invasive front was transformed in 28/136 gastric carcinoma cases. The transformation rate in highly differentiated tubular adenocarcinomas was the highest （51.5%, 17/33）. The deeper was the invasiveness, the higher was the transformation rate. The claudin-1 expression transformation rate in serosa and omenta was significantly higher （92.9%） than in tunica muscularis of invasive gastric cancer cases, as well as in patients with lymph node metastasis than in those without lymph node metastasis. CONCLUSION： Up-regulation of claudin-1 expression and its transformation in invasive and metastatic gastric carcinoma suggest that claudin-1 participates in the transformation of biological behaviors in neo- plasms. Further study is needed to elucidate the precise mechanism and the relation of claudin-1 expression with the neoplasm progress.     

Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer

In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinasetype plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P<.01) and lymph node metastasis (P<0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P<0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P<0.01), lymph node metastasis and depth of invasion (P<0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.     

DNA ploidy analysis and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma

AIM: To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. METHODS: Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16 cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node (LN) from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction (SPF) analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer. RESULTS: The expression of MMP-9 was significantly correlated with Lauren's classification, Borrmann's classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion (all P<0.05). The positive rate was lower in noncarcinoma than in carcinoma (31.3% vs66.7%, P<0.01). The expression of TIMP-2 was significantly correlated with Borrmann's classification, LN metastasis, and the depth of invasion (all P<0.05), The expression of E-cadherin was significantly correlated with differentiation, Lauren's classification, Borrmann's classification, and LN metastasis, as well as the depth of invasion (P<0,01 or P<0.05). E-cadherin was less expressed in carcinoma than in noncarcinoma (42.4% vs87.5%, P<0.01). There was a positive correlation between MMP-9 and TIMP-2 and a negative correlation between MMP-9 and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis. SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF. CONCLUSION: With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9, TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression.     

Relationship between preoperative staging by endoscopic ultrasonography and MMP-9 expression in gastric carcinoma

AIM： To investigate the relationship between the staging by endoscopic ultrasonography （EUS） and the expression of carcinoma metastasis associated gene in the patients with gastric carcinoma.
METHODS： Sixty-three patients with gastric cancer were diagnosed by electric gastroscopy and EUS. The preoperative staging of gastric cancer was measured by EUS and compared with pathologic staging and MMP-9 expression. Peripheral serum level of MMP-9 was measured with enzyme-linked immunosorbent assay （ELISA）, while the expression of MMP-9 protein was tested with immunohistochemistry and hybridization in situ in the gastric carcinoma tissues.
RESULTS： The total accuracy of EUS in estimating invasive depth of gastric cancer was 80.95%, while that in estimating lymphatic metastasis was 73.02%.Serum MMP-9 levels were consistent with the expression of MMP-9 protein and MMP-9 mRNA in tissue, a result closely correlated with invasive degree, staging with EUS and lymphatic metastasis in gastric cancer （P 〈 0.05）.The total accuracy of estimating invasive depth in gastric cancer was 95.22% using both EUS and MMP-9.
CONCLUSION： The MMP-9 level of preoperative serum presents the reference value for preoperative staging by EUS in the patients with gastric cancer. When serum MMP-9 level in gastric cancer is significantly high,physicians should pay closer attention to the metastasis which reaches the serosa or beyond. Combining EUS and MMP-9 improves the accuracy in deciding the invasion and metastasis in the patients with gastric carcinoma.     

Feasibility of endoscopic papillectomy in early stage ampulla of Vater cancer

Background and Aim:  Although endoscopic papillectomy has been attempted in early stage ampullary cancer (pTis, T1), its curative role and indications remain uncertain. The present study was designed to assess the factors that predict malignancy and lymph node metastasis and to suggest potential indications for endoscopic papillectomy by analyzing clinicopathological data.
Methods:  We performed a retrospective analysis of clinical and histopathological data of 216 patients with ampullary cancer between 1991 and 2006.
Results:  No tumor in pTis stage had metastasized to lymph nodes and only 9% of tumors in pT1 had metastasized. Tumor size ( P  = 0.018), depth of invasion ( P  = 0.021) and venous invasion ( P  = 0.014) were found to be significantly related to lymph node metastasis. Cases with early stage ampullary cancer of less than 2 cm with a well-differentiated histology and no angiolymphatic invasion ( n  = 13) showed no lymph node metastasis and no recurrence during a median follow up of 35.9 months.
Conclusion:  Endoscopic papillectomy can be adopted as a viable alternative to surgery in patients with early stage ampullary cancer of less than 2 cm in size and with a well-differentiated histology. When a resected specimen has a well-differentiated histology, and there is no resection margin involvement and no angiolymphatic invasion, our findings indicate that subsequent radical surgery is unnecessary.     

β-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: Relationships with carcinogenesis and metastasis

AIM: To investigate whether abnormal expression of β catenin in conjunction with overexpression of cyclinD1, cmyc and matrix metalloproteinase-7 (MMP-7) correlated with the carcinogenesis, metastasis and prognosis of pancreatic cancer, and to analyze the relationship of βcatenin expression with cyclinD1, c-myc and MMP-7 expression.METHODS: Using immunohistochemistry, we examined the expression of β-catenin, cyclinD1, c-myc and MMP-7 in 47 pancreatic adenocarcinoma tissues, 12 pancreaticintraepithelial neoplasia (PanIN) and 10 normal pancreases, respectively. Proliferation cell nuclear antigen was also tested as the index of proliferative activity of pancreatic cancer cells.RESULTS: In 10 cases of normal pancreatic tissues, epithelial cells showed equally strong membranous expression of β-catenin protein at the cell-cell boundaries, but the expression of cyclinD1, c-myc and MMP-7 was negative. The expression of β-catenin, cyclinD1, c-myc and MMP-7 in PanIN and pancreatic adenocarcinoma tissues had no significant difference [6/12 and 32/47 (68.1%), 6/12 and 35/47 (74.5%), 5/12 and 33/47 (70.2%), 7/12and 30/47 (63.8%), respectively]. The abnormal expression of β-catenin was significantly correlated to metastasis and one-year survival rate of pancreatic cancer, but had no relation with size, differentiation and cell proliferation. The expression of cyclinD1 was correlated with cell proliferation and extent of differentiation, but not with size, metastasis and one-year survival rate of the pancreatic cancer. The expression of c-myc was not correlated withsize, extent of differentiation, metastasis and 1-year survival rate, but closely with cell proliferation of pancreatic cancer. The overexpression of MMP-7 was significantly associated with metastasis and 1-year survival rate ofpancreatic cancer, but not with size, extent of differentiation and cell proliferation. There was a highly significant positive association between abnormal expression of β-cateninand overexpression of cyclinD1, c-myc and MMP-7 not only in PanIN (r = 1.000, 0.845, 0.845), but also in pancreatic cancer (r = 0.437, 0.452, 0.435).CONCLUSION: The abnormal expression of β-catenin plays a key role in the carcinogenesis and progression of human pancreatic carcinoma by up-regulaling the expression of cyclinD1, c-myc and MMP-7, resulting in the degradation of extracellular matrix and uncontrolled cell proliferation and differentiation. β-catenin abnormal expression and MMP-7 overexpression may be considered as two useful markers for determining metastasis and prognosis of human pancreatic cancer.     

Risk factors for lymph node metastasis and evaluation of reasonable surgery for early gastric cancer

AIM: To give the evidence for rationalizing surgical therapy for early gastric cancer with different lymph node status. METHODS: A series of 322 early gastric cancer patients who underwent gastrectomy with more than 15 lymph nodes retrieved were reviewed in this study. The rate of lymph node metastasis was calculated. Univariate and multivariate analyses were performed to evaluate the independent factors for predicting lymph node metastasis. RESULTS: No metastasis was detected in No.5, 6 lymph nodes (LN) during proximal gastric cancer total gastrectomy, and in No.10, 11p, 11d during for combined resection of spleen and splenic artery and in No.15 LN during combined resection of transverse colon mesentery. No.11p, 12a, 14v LN were proved negative for metastasis. The global metastastic rate was 14.6% for LN, 5.9% for mucosa, and 22.4% for submucosa carcinoma, respectively. The metastasis in group Ⅱ?was almost limited in No.7, 8a LN. Multivariate analysis identified that the depth of invasion, histological type and lymphatic invasion were independent risk factors for LN metastasis. No metastasis from distal cancer (≤ 1.0 cm in diameter) was detected in group Ⅱ?LN. The metastasis rate increased significantly when the diameter exceeded 3.0 cm. All tumors (≤ 1.0 cm in diameter) with LN metastasis and mucosa invasion showed a depressed macroscopic type, and all protruded carcinomas were > 3.0 cm in diameter. CONCLUSION: Segmental/subtotal gastrectomy plus D1/D1 No.7 should be performed for carcinoma (≤ 1.0 cm in diameter, protruded type and mucosa invasion).Subtotal gastrectomy plus D2 or D1 No.7, 8a, 9 is the most rational operation, whereas No.11p, 12a, 14v lymphadenectomy should not be recommended routinely for poorly differentiated and depressed type of submucosa carcinoma (> 3.0 cm in diameter). Total gastrectomy should not be performed in proximal, so does combined resection or D2 /D3 lymphadenectomy.     

Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9

Aim:  To investigate the status of Phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mammalian target of rapamycin (mTOR) pathway and its correlation with clinicopathological features and matrix metalloproteinase-2, -9 (MMP-2, 9) in human hepatocellular carcinoma (HCC).
Methods:  PTEN, Phosphorylated AKT (p-AKT), Phosphorylated mTOR (p-mTOR), MMP-2, MMP-9 and Ki-67 expression levels were evaluated by immunohistochemistry on tissue microarrays containing 200 HCCs with paired adjacent non-cancerous liver tissues. PTEN, MMP-2 and MMP-9 mRNA levels were determined by real-time RT-PCR in 36 HCCs. The relationships between PI3K/PTEN/AKT/mTOR pathway and clinicopathological factors and MMP-2, 9 were analyzed in HCC.
Results:  In HCC, PTEN loss and overexpression of p-AKT and p-mTOR were associated with tumor grade, intrahepatic metastasis, vascular invasion, TNM stage and high Ki-67 labeling index ( P  < 0.05). PTEN loss was correlated with p-AKT, p-mTOR and MMP-9 overexpression. Furthermore, PTEN and MMP-2, 9 mRNA levels were down-regulated and up-regulated in HCC compared with paired non-cancerous liver tissues, respectively ( P  < 0.01). PTEN, MMP-2 and MMP-9 mRNA levels were correlated with tumor stage and metastasis. There was an inverse correlation between PTEN and MMP-9 mRNA expression. However, PI3K/PTEN/AKT/mTOR pathway was not correlated with MMP-2.
Conclusions:  PI3K/PTEN/AKT/mTOR pathway, which is activated in HCC, is involved in invasion and metastasis through up-regulating MMP-9 in HCC.     

EVALUATION OF THE RISK FACTORS OF LYMPH NODE METASTASIS IN PT1 STAGE COLORECTAL CARCINOMA: INDICATION FOR AN ENDOSCOPIC MUCOSAL RESECTION

Aim: In the present study, we aimed to clarify the parameters that can be used for clinically relevant treatment decisions. Patients and methods: During the period from July 1985 to April 2005, 283 pT1 cancers were selected for this study. Risk factors for lymph node (LN) metastasis were evaluated as follows: endoscopic appearance, tumor size, location, lymphatic permeation, venous invasion, patterns of cancer invasion into the submucosal layer, and depth of vertical invasion in the submucosal layer. Results: Results of the logistic regression analysis from these significant parameters were as follows: infiltrating growth pattern (odds ratio: 12.63); lymphatic permeation positive (odds ratio: 5.726); sigmoid colon (odds ratio: 4.585); tumor size (odds ratio: 1.718). However, the leading edge of only one cancer with LN metastasis in the expanding growth group was also cribriform pattern. Conclusion: The invasive growth patterns of infiltrating growth, lymphatic permeation, tumor location of the sigmoid colon, and maximum tumor size were independent and significant risk factors for LN metastasis in our logistic regression analysis. In particular, the former three factors (infiltrating growth, lymphatic permeation and sigmoid colon) revealed high odds ratio and covered all cases of LN metastasis. From the results of our study, the indication for operative intervention after EMR in pT1 cancer is those lesions which possess at least one factor among the three (infiltrating growth, lymphatic permeation and sigmoid colon). Also, assessment of the leading edge with a cribriform pattern should be dealt with carefully.     

MMP-9、HPSE和VEGF-C蛋白表达在中老年人肺癌抗血管和抗淋巴管生成治疗中的意义

目的探讨基质金属蛋白酶9(MMP9)、乙酰肝素酶(HPSE)和血管内皮生长因子C(VEGFC)蛋白表达在中老年人肺癌抗血管和抗淋巴管生成治疗中的意义。方法应用免疫组化SABC法检测MMP9、HPSE和VEGFC蛋白表达在65例肺癌组织中的表达,并与癌旁组织和正常肺组织对比,同时结合肺癌的临床病理学特征及预后进行分析。结果肺癌组织中MMP9、HPSE和VEGFC蛋白的阳性表达率明显高于正常肺组织和癌旁组织(P<005);不同类型和不同分化程度肺癌组织中MMP9、HPSE和VEGFC蛋白阳性表达率无显著性差异(P>005);Ⅲ期和Ⅳ期肺癌组织中MMP9、HPSE和VEGFC蛋白阳性表达率明显高于Ⅰ期和Ⅱ期(P<005);生存3年以下的肺癌组织中MMP9、HPSE和VEGFC蛋白阳性表达率明显高于生存3年以上者(P<005)。结论MMP9、HPSE蛋白表达在肺癌的生长、侵袭和转移以及血管生成中发挥重要作用;VEGFC是促进肺癌经淋巴转移的重要因素;肺癌的生长、侵袭和转移可能是MMP9、HPSE促血管生成和VEGFC促淋巴生成二者的协同作用;MMP9、HPSE和VEGFC蛋白可作为判断肺癌生物学行为和患者预后的一个参考指标;为人肺癌抗血管和抗淋巴管生成治疗的可行性提供了一定的实验依据。     

Immunohistochemical molecular markers as predictors of curability of endoscopically resected submucosal colorectal cancer

AIM： To clarify the usefulness of immunohistochemical molecular markers in predicting lymph node metastasis of submucosal colorectal cancer.
METHODS： We examined microvessel density, lymphatic vessel density, the Ki-67 labeling index, expression of MUC1 and Matrix metalloproteinase-7 （MMP-7） in tumor cells, and expression of cathepsin D in stromal cells at the invasive front by immunostaining of samples resected from 214 patients with submucosal colorectal cancer. Pathologic features were assessed on hematoxylin-eosinstained samples. We evaluated the relations between clinicopathologic/immunohistochemical features and lymph node metastasis.
RESULTS： Lesions of the superficial type, with an unfavorable histologic grade, budding, lymphatic involvement, high microvessel density （≥ 40）, high lymphatic vessel density （≥9）, high Ki-67 labeling index （≥ 42）, and positivity of MUC1, cathepsin D, and MMP-7 showed a significantly high incidence of lymph node metastasis. Multivariate analysis revealed that high microvessel density, unfavorable histologic grade, cathepsin D positivity, high lymphatic vessel density, superficial type, budding, and MUC1 positivity were independent risk factors for lymph node metastasis.A combined examination with four independent immunohistochemical markers （microvessel density, cathepsin D, lymphatic vessel density, and MUC1） revealed that all lesions that were negative for all markers or positive for only one marker were negative for lymph node metastasis.
CONCLUSION： Analysis of a combination of immuno- histochemical molecular markers in endoscopically resected specimens of submucosal colorectal cancer allows prediction of curability regardless of the pathologic features visible of hematoxylin-eosin-stained sections.     

结肠癌组织中MMP-7、MMP-9的表达及意义

目的观察结肠癌组织中基质金属蛋白酶（MMP）-7、MMP-9的表达，探讨其在结肠癌浸润、转移中的作用。方法采用免疫组化SP法检测50例结肠癌及其切缘组织中MMP-7、MMP-9的表达。结果肿瘤组织中MMP-7、MMP-9阳性表达率分别为68．00％和82．00％，标本切缘组织中分别为0和24．00％，两者相比，P均〈0．05，MMP-7、MMP-9在有淋巴结转移者中的阳性表达率为86．96％和91．30％，显著高于无淋巴结转移者的51．85％和74．07％，P均〈0．05；MMP-7、MMP-9在结肠癌组织中的表达呈正相关，r=0．84，P〈0．05。结论MMP-7、MMP-9高表达可能与结肠癌的浸润、转移有关。     

The expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs) and angiogenesis in relation to the depth of tumor invasion and lymph node metastasis in submucosally invasive colorectal carcinoma]

BACKGROUND/AIMS: Lymph node (LN) metastasis occurs in approximately 10% of patients with submucosally invasive colorectal carcinoma. This study was performed to determine the role of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) production and microvessel formation on the LN metastasis in submucosally invasive colorectal carcinoma. METHODS: A total of forty-one subjects with surgically resected submucosally invasive colorectal carcinoma were included in this study. Immunohistochemical staining of MMP-2, MMP-9, TIMP-1, TIMP-2, and urokinase-type plasminogen activator were performed. Angiogenesis was evaluated by counting the number of microvessels in each pathologic specimen as identified by CD34 immunohistochemical staining. RESULTS: The depth of submucosal invasion was not significantly correlated with the expression of MMP-2, MMP-9, TIMP-1, TIMP-2, or urokinase-type plasminogen activator, but the microvessel count was significantly correlated with the absolute depth of invasion (r=0.312, p<0.05). Upregulation of TIMP-2 was positively correlated with adjacent lymphatic invasion (p<0.05) and increased TIMP-2 expression was correlated with LN metastasis in submucosally invasive colorectal carcinoma (p=0.088). CONCLUSIONS: These results suggest that the expression of TIMP-2 and the microvessel count may be useful parameters for considering additional surgery after endoscopic treatment of submucosally invasive colorectal carcinoma.     

A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer

Purpose Matrix metalloproteinase-9 (MMP-9, gelatinase B) plays a key role in cancer invasion and metastasis by degradating the extracellular matrix (ECM) and basement membrane barriers. A cytosine (C)-thymidine (T) single nucleotide polymorphism (SNP) at position –1562 in the MMP-9 promoter is reported to affect expression of this gene. The purpose of this study was to investigate the relation between the –1562 C/T polymorphism and the development and progression of gastric cancer.Methods The study population included 177 gastric cancer patients and 224 healthy control subjects. The SNP in the MMP-9 promoter was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Genotype frequencies were compared between patients and controls, and the association of genotypes with clinicopathological features was studied.Results Genotype frequencies in gastric cancer patients were similar to those in control subjects (P = 0.223). However, significant association was found between degree of tumor invasion, clinical stage, and lymphatic invasion and the MMP-9 polymorphism in gastric cancer patients (P<0.05, for each).Conclusions Our results indicate that the T allele in the MMP-9 promoter is associated with the invasive phenotype of gastric cancer.     

CD10 Expression in Colorectal Carcinoma Correlates With Liver Metastasis

PURPOSE If it were possible to identify the features of primary colorectal carcinoma that were associated with liver metastasis, these features could be used as predictors of liver metastasis. METHODS From January 1995 to December 1997, 648 consecutive cases of colorectal carcinoma were recorded at the Department of Surgery, National Cancer Center Hospital, Tokyo, Japan. We evaluated clinicopathologic and immunohistochemical factors (age, gender, tumor location, gross type, size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and expression of CD10, MUC2, and human gastric mucin) in 505 of these patients who had undergone resection of T2/T3/T4 colorectal carcinomas to clarify the correlation between these factors and liver metastasis. RESULTS Liver metastases, including unresectable, were detected in 122 patients (24 percent), all of whom had been followed for at least five years. Univariate analysis revealed that liver metastasis was significantly associated with tumor size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and CD10 expression. Multivariate analysis revealed that invasion deeper than the subserosa, venous invasion, lymph-node metastasis, and CD10 expression were significantly associated with liver metastases. CONCLUSIONS CD10 expression in colorectal carcinoma is a good predictor of liver metastasis. Supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare, Japan.     

Claudin-4 mRNA在胃癌组织中的表达及其临床意义

目的 研究chudin-4mRNA在胃癌组织中的表达,并探讨其与胃癌生物学行为的关系.方法 应用半定量逆转录聚合酶链反应(RT-PCR)检测10例正常胃黏膜组织和31例胃癌组织的claudin-4 mRNA的转录水平.结果 正常胃黏膜组织claudin-4 mRNA相对表达量低于胃癌组织(P<0.05),高中分化胃癌组织低于低分化组织(P<0.05),有淋巴结转移的胃癌组织高于无淋巴结转移组织(P<0.05),浸润深度达黏膜下层组织高于浸润深度未达到者(P<0.05).claudin-4 mRNA相对表达量与患者性别及肿瘤大小无显著相关性(P>0.05).结论 Claudin-4 mRNA在胃癌中表达上调可能在胃癌的发生发展中起着重要的作用,其表达上调可能促进胃癌的侵润和转移.     

人源幼虫巨大致死性基因在胃癌组织中的表达及意义

目的研究人源幼虫巨大致死性基因（Hud—1）在胃癌中的表达及其与胃癌临床病理特征的关系,探讨Hugl-1改变与胃癌发生及进展的相关性。方法采用免疫组化SP法检测81例胃癌标本和14例胃良性病变标本nugl-1的表达情况,并结合临床病理参数进行相关分析。结果胃癌组织中Hud．1的表达水平明显低于正常组织及炎性胃组织,部分表达缺失。81例胃癌组织中Hugl-1表达下调54例,总下调率为66．7％。Hugl-1的阳性表达率与患者的年龄、癌细胞分化程度及有无淋巴结转移相关（P〈0．05）,与性别及浸润深度则无明显相关（P〉0．05）。结论Hugl-1表达下调与胃癌的发生、发展过程密切相关,Hugl-1可作为反映胃癌恶性生物学行为的一个较有价值的指标。     

Factors affecting recurrence in node-negative advanced gastric cancer

Background and Aim:  Prognostic factors of lymph node-negative gastric adenocarcinoma after curative resection have been discussed. Recurrent pattern of advanced lymph node-negative gastric cancer after curative resection has rarely been described.
Methods:  Recurrent sites and correlated clinicopathological factors of 372 patients with lymph node-negative advanced gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were analyzed.
Results:  Recurrence was noted in 51 (13.7%) patients. Recurrent rates according to site of recurrence were 26 peritoneal seeding (51.0%), 26 locoregional (51.0%), 17 hematogenous (33.3%), and 4 lymph node metastasis (7.8%). Clinicopathological factors to predict peritoneal seeding were serosal exposure, lymphovascular invasion, Lauren's diffuse type differentiation and scirrhous stromal reaction. Serosal exposure, tumor size, microscopic infiltrating growth type predicts locoregional recurrence. Tumor had only lymphovascular invasion predict hematogenous spreading.
Conclusion:  Node-negative advanced gastric cancer has more peritoneal seeding and locoregional recurrence. Aggressive cell behavior predicted the route of tumor cell spreading.