血管内皮生长因子-D在胃癌中表达的意义

Objective： To investigate the expression of vascular endothelial growth factor D （VEGF-D） in gastric cancer and its relationship with lymph node metastasis. Methods： 100 cases of gastric carcinoma tissues （50 cases with lymph node metastasis, 50 cases negative） and 30 cases of normal gastric tissues were gathered to detect the expressions of VEGF-C and D proteins by immunohistochemistry. Results： VEGF-C and D were revealed in cytoplasm of gastric carcinoma tissues and normal gastric tissues. The positive rates of VEGF-C and D expressions were significantly higher in gastric cancer tissues than those in the normal ones （51%, 60% vs 10%, 20% respectively; both P 〈 0.05）. There were significant correlations between the positive expression of VEGF-D and lymph node metastasis, lymphatic invasion, positive expression of VEG F-C, but not with tumour size, tissue differentiation, and venous invasion. Conclusion： The expression of VEGF-D is closely related to lymph node metastasis in gastric carcinoma.     

Reduction of CAII expression in gastric cancer: Correlation with invasion and metastasis

Objective: Human carbonic anhydrases II (CAII) gene plays an important role in different cancer. However, its relevance to gastric cancer (GC) remains unclear. In the present study, we aimed to investigate the expression of CAII in GC and explore its correlation with some clinicopathologic characteristics of GC. Methods: The expression of CAII in 20 specimens of normal gastric mucosa, 38 specimens of intraepithelial neoplasia and 112 specimens of gastric carcinoma were detected by immunohistochemical techniques. Survival in GC with CAII expression was studied. Results: The positive rate of CAII protein in normal gastric mucosa was significantly higher than that in intraepithelial neoplasia and gastric carcinoma (100% vs. 63.16% and 28.57%, P<0.001). The positive rate of CAII protein was significantly higher in gastric carcinoma at early stages than that at advanced stages (70.0% vs. 19.57%, P<0.001). The positive rate of CAII protein was significantly lower in gastric carcinoma with lymph node metastases than that without lymph node metastases (10.81% vs. 37.33%, P<0.05). Furthermore, the positive rate of CAII protein was significantly lower in poorly-differentiated gastric carcinoma than in moderately- or well-differentiated gastric carcinoma (15.94% vs. 31.03% or 60.00%, P<0.05). Moreover, CAII expression was not related with sex, age and tumor size. The patients with CAII-positive tumors showed a better survival rate than those with CAII-negative tumors (P=0.024, log-rank test). Conclusion: CAII expression was related with stages and lymph node metastases in gastric carcinoma. The reduction of CAII expression in GC might promote tumor cell motility and contribute to tumor growth and metastasis.     

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.     

Expression and clinical significance of REGγ in gastric cancer tissue and variously differentiated gastric cancer cell lines

OBJECTIVE To evaluate the REGγ expression in gastric cancer tissue and gastric cancer cell lines of various differentiation levels and its clinical significance. METHODS Immunohistochemistry was used to detect the expression of REGγ protein in 70 specimens of gastric cancer and 30 specimens of normal gastric mucosa. The relationship between the expression of REGγ protein and the biological behaviors of gastric cancer was analyzed. RT-PCR and Western blot were used to detect the mRNA level and the protein expression of REGγ in normal gastric cell line GES-1, well differentiated gastric cancer cell line MKN-28, moderately differentiated gastric cancer cell line SGC-7901 and poorly differentiated gastric cancer cell line BGC-823. RESULTS The expression rate of REGγ protein in gastric cancer tissue （52/70, 74.29%） was significantly higher than that in normal gastric tissue （12/30, 40%） （P 〈 0.01）. The expression rate of REGγ was correlated with tumor size （P 〈 0.01）, lymph node metastasis （P 〈 0.05）, differentiation degree （P 〈 0.01）, infiltration depth （P 〈 0.01） and distant metastasis （P 〈 0.05）. RT-PCR analysis showed that the expression of REGγ mRNA was 0.459 ± 0.079 in the normal gastric mucosa cell ling 0.588 ±0.118 in the well differentiated gastric cancer cell line, 0.715±0.066 in the moderately differentiated gastric cancer cell line, and 0.873 ± 0.099 in the poorly differentiated gastric cancer cell line, showing a negative correlation between REGγ mRNA expression and differentiation level （P 〈 0.05）. Western blot analysis showed that the expression of REGγ protein was 0.712±0.065 in the normal gastric mucosa cell line, 1.176±0.185 in the well differentiated gastric cancer cell line, 1.533 ± 0.127 in the moderately differentiated gastric cancer cell line, and 2.061± 0.398 in the poorly differentiated gastric cancer cell line, showing a negative correlation between REGγ protein expression and differentiation level （P 〈 0.05）. CONCLUSION REGγ is expressed in gastric cancer tissue and normal gastric tissue. In gastric cancer tissues, REGγ expression is positively correlated with the tumor size, lymph node metastasis, differentiation degree, infiltration depth and distant metastasis. Detecting the expression of REGγ mRNA and protein is helpful for early diagnosis and predicting prognosis of gastric cancer.     

Expression and Clinical Significance of REGy in Gastric Cancer Tissue and Variously Differentiated Gastric Cancer Cell Lines

OBJECTIVE To evaluate the REGy expression in gastric cancer tissue and gastric cancer cell lines of various differentiation levels and its clinical significance.METHODS Immunohistochemistry was used to detect the expression of REGy protein in 70 specimens of gastric cancer and 30 specimens of normal gastric mucosa. The relationship between the expression of REGy protein and the biological behaviors of gastric cancer was analyzed. RT-PCR and Western blot were used to detect the mRNA level and the protein expression of REGγ in normal gastric cell line GES-1, well differentiated gastric cancer cell line MKN-28, moderately differentiated gastric cancer cell line SGC-7901 and poorly differentiated gastric cancer cell line BGC-823.RESULTS The expression rate of REGγprotein in gastric cancer tissue (52/70, 74.29%) was significantly higher than that in normal gastric tissue (12/30, 40%) (P<0.01). The expression rate of REGywas correlated with tumor size (P<0.01), lymph node metastasis (P<0.05), differentiation degree (P<0.01), infiltration depth (P<0.01)and distant metastasis (P<0.05). RT-PCR analysis showed that theexpression of REGγ mRNA was 0.459±0.079 in the normal gastric mucosa cell line, 0.588±0.118 in the well differentiated gastric cancer cell line, 0.715±0.066 in the moderately differentiated gastric cancer cell line, and 0.873±0.099 in the poorly differentiated gastric cancer cell line, showing a negative correla- tion between REGγmRNA expression and differentiation level (P <0.05). Western blot analysis showed that the expression of REGy protein was 0.712±0.065 in the normal gastric mucosa cell line, 1.176±0.185 in the well differentiated gastric cancer cell line, 1.533 ±0.127 in the moderately differentiated gastric cancer cell line, and 2.061±0.398 in the poorly differentiated gastric cancer cell line, showing a negative correlation between REGγprotein expression and differentiation level (P<0.05).CONCLUSION REGγ is expressed in gastric cancer tissue and normal gastric tissue. In gastric cancer tissues, REGγexpression is positively correlated with the tumor size, lymph node metastasis,differentiation degree, infiltration depth and distant metastasis. Detecting the expression of REGy mRNA and protein is helpful for early diagnosis and predicting prognosis of gastric cancer.     

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.     

STAT1 and Survivin Expression in Full Lymph Node Examined Gastric Cancer by Using Tissue Microarray Technique

Objective： To characterize the relationship between STAT1 and Survivin expression, and the relationship between them and lymph node metastasis, depth of invasion and prognosis in full lymph node examined gastric cancer patients of China. Methods： Specimens of curative dissection between 1988 and 2003 were collected from the affiliated hospital of Jianghan University. All 140 patients had complete examination data. All lymph nodes were found by clearing fat method. The interrupted serial 4 μm sections, routine hematoxylin and eosin staining and immunohistochemical methods were used to detect the lymph node metastases. Gastric cancer tissue microarray was formed and the expression of survivin and STAT1 in gastric cancer was detected by immunohistochemical method. All data were processed using Spearman rank correlation analysis, Kaplan-Meyer Log-rank method and Cox multivariate analysis （SPSS 12.0 software）. Results： Among 140 gastric cancer tissue microarrays constructed, 110 could be used （utilization rate was 78.6%）. 7079 lymph nodes were found in 110 cases （64.4/case）. Metastases were found in 89 cases and 1679 lymph nodes. Positive expression rate of survivin and STAT1 was 52.7% （58/110） and 40% （44/110） respectively. There was a significant negative correlation between STAT1 expression and survivin expression （r=-0.19, P=0.04）. STAT1 expression had a negative correlation with depth of invasion （r=0.21, P=0.04）. Survivin expression had a negative correlation with UICC N stage （r=-0.24, P=0.01） and histological classification （r=-0.21, P=0.03） by Spearman rank correlation analysis. But survivin and STAT1 expression was not related with prognosis. A significant correlation between lymph node metastasis and prognosis was demonstrated by Cox multivariate analysis （X^2=4.85, P=0.028）. Conclusion： STAT1 has a negative correlation with survivin expression in gastric cancer. Both of them have no correlation with prognosis in gastric cancer. STAT1 expression can be a molecular marker to predict advanced gastric cancer and survivin a molecular marker of lymph node metastasis in gastric cancer. UICC N stage is the most important prognostic factor in gastric caner in China.     

E-钙黏蛋白在鼻咽癌组织中的表达水平及其与颈部淋巴结转移的关系

Objective To investigate the expression of E-cadherin in nasopharyngeal carcinoma ( NPC) and its relationship with cervical lymph node metastasis. Methods The expression of E-cadherin in 80 patients with NPC was detected by immunohistochemistry. Results Lower expression of E-cadherin was associated with advanced N-stage of the tumor ( P = 0. 018 ). There was no significant correlation between the expression of E-cadherin and lymph node size ( P = 0.435 ). The expression of E-cadherin was higher in patients with cervical lymph node metastasis limited to a single area than that distributing in some scattered areas (P = 0. 000). There was a trend that the expression of E-cadherin in the cases with the tumor and lymph nodes in the same side was higher (56. 5% ) than that in the patients with bilateral lymph node metastases (32. 6% ) , however, the difference was not significant (P =0. 059). The expression rates of E-cadherin in patients with lymph node metastasis in levels Ⅱ , Ⅲ and Ⅴa were higher than that in levels Ⅰ , Ⅳ, Vb and Ⅵ, but with a non-significant difference (P = 0.059). Conclusion The expression of E-cadherin has influence on the lymph node metastasis in nasopharyngeal carcinoma. E-cadherin expression is negatively correlated with the numbers of the lymph node metastases and the metastasis distance, i. e. a lower expression of E-cadherin leads to an advanced N-stage. The lymph node metastasis of nasopharyngeal cancer from above to below is more considerably influenced by E-cadherin expression than the metastasis towards contralateral lymph nodes.     

EphB2受体在胃癌中的表达变化及其与转移的关系

目的：观察EphB2在胃癌和转移灶中的表达,并探讨它们在肿瘤发生、发展和转移中的作用以及与胃癌的临床病理参数的关系。方法：采用组织芯片和免疫组化方法检测EphB2在正常粘膜（n=71）、原发癌（n=71）、淋巴结转移癌（n=71）和远处转移癌（n=26）中的表达,比较它们在原发灶和正常组织、转移灶的表达差异。结果：EphB2的表达随肿瘤的发生和进展逐渐下降。EphB2在正常粘膜、原发癌、淋巴结转移和器官远处转移中的表达率分别为：83．1％（59／71）、60．6％（43／71）、43．7％（31／71）和26．9％（7／26）。正常粘膜组织中EphB2的表达率显著高于肿瘤细胞中的表达（P〈0．01）。脏器转移中的表达又显著低于原发癌中的表达（P=0．003）。原发灶和转移灶中EphB2表达不一致的病例数与性别（男性）和浸润深度高度相关（P〈0．05）。结论：肿瘤转移是一个遗传改变逐步积累的结果,EphB2表达下调在胃癌发展及转移中可能起重要作用。     

S100A4蛋白表达与胃癌侵袭转移关系的研究

目的：探讨Ｓ１００Ａ４蛋白产与胃癌侵袭转移的关系。方法：应用免疫组织化学方法检测６２例胃癌患者的胃癌组织和３８例癌旁正常粘膜、２３例淋巴结转移癌及胃癌纱ＭＫＮ４５、ＢＧＣ８２３中Ｓ１００Ａ４蛋白表达,Ｂｏｙｄｅｎ小室法检测胃癌细胞侵袭能力。结果：胃癌组织Ｓ１００Ａ４表达阳性率（７０．５９％）显著高于癌旁正常粘膜（１５．７９％）（Ｐ〈０．０１）。在弥温生长、低分化及未分化型、浸透浆膜、淋巴结转移阳性     

胃癌组织中钙粘附蛋白-E和S100A2表达与其临床生物学行为关系的研究

研究胃癌组织中粘附蛋白-E（E-cadherin）和S100A2的表达,及其与胃癌的临床生物学行为的关系。方法：采用半定量RT-PCR方法及免疫组织化学（IHC）法,检测辽宁省肿瘤医院2006年7至12月收治的不同分期胃癌组织标本,配对癌旁组织及正常胃黏膜组织检测E-cadherin和S100A2的表达情况,分析与肿瘤临床特征的相关性及其在胃癌进展中的作用。结果： E-cadherin和S100A2扩增产物长度分别为487 bp和362 bp。E-cadherin及S100A2基因在正常对照组胃黏膜织表达阳性率为100%,不同分期胃癌组织基因表达的阳性率均下降。两者在正常胃黏膜中蛋白表达阳性率为100%,在胃癌组织中蛋白表达阳性率下降。两者在胃癌中表达的一致性较高,在胃癌的大体分型、分化程度、浸润深度及淋巴结转移等临床特征中,蛋白阳性表达率差异有统计学意义。结论：E-cadherin和S100A2在胃癌组织中表达均下降,是肿瘤抑制因子,其表达与胃癌的分化、转移、侵袭呈负相关。     

S100A4蛋白在非小细胞肺癌中的表达与侵袭和转移的关系

背景与目的:实验证明S100A4在多种恶性肿瘤细胞中高表达,它可能在恶性肿瘤细胞的侵袭和转移等过程中发挥重要作用。本研究探讨S100A4在人非小细胞肺癌中的表达及其与侵袭和转移的关系。方法:采用免疫组化SP法检测41例非小细胞肺癌及6例正常肺组织中S100A4蛋白的表达水平。结果:S100A4在非小细胞肺癌中的阳性率(70.7%)显著高于正常肺组织(16.7%)(P<0.05);在肺腺癌中的阳性率(90.0%)明显高于肺鳞癌(52.4%)(P<0.01)。在TNM分期中,S100A4在Ⅲ Ⅳ期、Ⅱ期和Ⅰ期的阳性率分别为100.0%、66.7%和30.0%,Ⅲ Ⅳ期明显高于Ⅱ期和Ⅰ期(P<0.01),但是Ⅱ期和Ⅰ期间无显著性差异(P>0.05)。S100A4的阳性率在有淋巴结转移的非小细胞肺癌中(90.0%)明显高于无淋巴结转移组(52.4%)(P<0.01),且S100A4的表达与淋巴结转移密切相关(r=0.480,P=0.001)。肿瘤体积增大(<3cm,≥3cm),S100A4的阳性率明显升高(44.4%,91.3%)(P<0.001),且相关性显著(r=0.288,P=0.017)。S100A4的阳性率与非小细胞肺癌的病理分级无明显相关性(P>0.05)。结论:S100A4在非小细胞肺癌中的表达上调,且与淋巴结转移、TNM分期和肿瘤大小密切相关,提示S100A4与非小细胞肺癌的侵袭和转移有关。     

The expression of CXCL12 and CXCR4 in gastric cancer and their correlation to lymph node metastasis

The purpose of this study was to investigate the expression of CXCL12 and its receptor CXCR4 in gastric cancer and to determine their relationship with lymph node metastasis. Fifty patients with pathologically confirmed gastric cancer were analyzed from September 2004 to December 2004. The expression levels of CXCL12 and CXCR4 were examined by immunohistochemical staining in the primary gastric tumor tissues, adjacent normal mucosa tissues, and metastatic lymph nodes and were analyzed along with clinicopathological risk factors, to determine their correlation with the prognosis. Positive staining for CXCL12 and CXCR4 was identified in 90.0 and 80.0% of the primary gastric tumor tissues, respectively, with significantly higher expression intensities observed in the primary gastric tumor tissues than in the adjacent normal mucosa tissues (P?<?0.01 and P?=?0.01, respectively). Positive staining for CXCL12 and CXCR4 was identified in 94.4 and 91.7% of metastatic lymph nodes, respectively, with significantly higher expression intensities in the metastatic lymph nodes than in the adjacent normal mucosa tissues (P?<?0.01 and P?=?0.01, respectively). Expression of CXCL12 in the primary gastric tumor tissues was not significantly associated with the clinicopathological characteristics of the tumor or the disease prognosis. However, the intensity of CXCR4 staining in primary tumor tissues was positively related with lymph node metastasis, TNM staging, and disease prognosis (P?=?0.04, 0.03, 0.03, respectively). CXCL12 and CXCR4 are related to formation of gastric tumors and lymph node metastasis. Furthermore, the expression of CXCR4 could be used as a biomarker to predict malignant features of gastric cancer.     

趋化因子受体CXCR4/CXCL12信号转导通路与胃癌淋巴结转移关系的研究

目的:检测趋化因子受体CXCR4/CXCL12信号转导通路在胃癌组织、远癌正常粘膜以及转移淋巴结中的表达情况,分析CXCR4/CXCL12在胃癌淋巴结转移中的作用。方法:应用Western blot检测胃癌组织中CXCR4/CXCL12通路成员表达。结果:胃癌组织中CXCR4/CXCL12表达水平明显高于正常胃粘膜(P<0.05);32例淋巴结转移癌组织中22例CXCR4/CXCL12蛋白表达高于原发癌;CXCR4/CXCL12表达水平与淋巴结转移有关(P(0.05)。结论:趋化因子受体CXCR4/CXCL12在原发胃癌及其淋巴结转移癌组织中均呈高表达,CXCR4信号转导通路可能在胃癌淋巴结转移过程中起重要作用。     

KiSS-1、KiSS-1受体GPR54及基质金属蛋白酶-9与非小细胞肺癌侵袭转移的关系

目的：研究KiSS-1、KiSS-1受体GPR54及基质金属蛋白酶-9（MMP-9）在非小细胞肺癌组织中的表达及其与非小细胞肺癌侵袭转移的关系,探讨三者在非小细胞肺癌侵袭转移中是否具有相关性。方法：选择98例原发性非小细胞肺癌癌组织及30例癌旁肺组织的标本,采用链霉素抗生物素蛋白-过氧化物免疫组化法（S-P法）检测组织中KiSS-1、GPR54及MMP-9的表达情况。结果：KiSS-1在非小细胞肺癌组织中的表达显著低于癌旁肺组织（P〈0.01）;MMP-9在非小细胞肺癌组织中的表达显著高于癌旁肺组织中的表达（P〈0.01）。KiSS-1在有淋巴结转移的非小细胞肺癌中的表达显著低于无淋巴结转移者（P〈0.01）;MMP-9在有淋巴结转移的非小细胞肺癌组织中的表达显著高于无淋巴结转移者（P〈0.05）。KiSS-1与GPR54、MMP-9在肺癌组织中的表达均具有负相关性（P〈0.05）。结论：KiSS-1基因表达下调和GPR54、MMP-9蛋白过表达与非小细胞肺癌的侵袭转移密切相关。     

早期胃癌组织中上皮钙粘蛋白表达与淋巴结微转移及临床病理的关系

背景与目的:早期胃癌淋巴结微转移问题日益受到关注,胞浆角蛋白(cytokeratin,CK)染色是识别上皮源性恶性肿瘤细胞的重要方法,本研究拟探讨早期胃癌原发灶上皮钙粘蛋白(epithelial cadherin,E-cad)的表达情况与淋巴结内出现微转移之间的关系及临床意义.方法:用免疫组织化学染色的方法对162例早期胃癌患者的4 522枚淋巴结进行苏木精-伊红(HE)和胞浆角蛋白(cytokeratin,CK)染色,并对其中135例患者的原发灶切片进行E-cad染色,结合临床病理资料和随访结果进行分析.结果:HE染色发现的淋巴结转移率为6.8%(11/162),而CK染色发现的淋巴结转移率为26.5%(43/162),二者差异有统计学意义(P＜0.001).在151例HE染色未见淋巴结转移的患者中通过CK染色发现了32例(21.2%)有淋巴结微转移,且淋巴结微转移多见于原发灶直径大于1.0 cm,组织分化不良,肿瘤浸润较深的(如浸及粘膜下层),淋巴管和血管受累,以及E-cad低表达标本(P＜0.05).原发灶E-cad的低表达率为57.0%(77/135),与淋巴结出现微转移有密切关系,有淋巴结微转移患者的5年生存率比没有微转移者明显低(P＜0.01).结论:肿瘤直径大于1.0 cm,组织分化不良,较深的浸润,淋巴管或血管受累,以及E-cad低表达是早期胃癌患者出现淋巴结转移的高危因素.     

Development of new spontaneous metastatic heterotopic model of lewis lung carcinoma imaged by GFP expression

Many studies have demonstrated the importance of spontaneous metastases in cancer research. Until now, we still had only a few spontaneous metastatic models with high occurrence rate of metastasis in distant lymph and visceral tissues. We report a syngeneic heterotopic metastatic model using the Lewis lung cancer cell line with high metastatic ratio in C57BL/6 mice after transplantation by injection of cancer cells and without surgical intervention. Metastatic process was declared for each mouse in two groups ?sacrificed 3 or 5 weeks after subcutaneous (s.c.) injection of the tumor cells into the dorsal side of the tail. The total number of metastases was counted as the sum of observed macrometastases. Our model produced produced a 100% rate of spontaneous lymphatic and visceral metastases after a simple injection transplantation into the heterotopic site. In mice with large primary tumors which are non-lethal, visceral and lymph macrometastases were observed. Tumor volume correlated linearly not only with the tumor growth time, but also with the number of metastases in lymph nodes and organs. This new metastatic model could be useful for studying the metastasis mechanism and for developing therapy for lymph and visceral metastases.     

Co-expression of osteopontin and CD44v9 in gastric cancer

We have examined the expression of osteopontin (OPN) in 40 human primary gastric carcinoma tissues, 5 metastatic foci (lymph nodes) and corresponding normal mucosas. Twenty-nine of 40 primary tumors (72.5%) and 3 of 5 lymph node metastases (60%) overexpressed OPN mRNA in comparison with those of the corresponding normal mucosa. The incidence as well as relative expression level of OPN mRNA was higher in well differentiated gastric cancers than poorly differentiated ones. Moreover, increased OPN mRNA expression in primary tumor specimens was observed along with the advancement of the clinico-pathological stage. Using in situ hybridization (ISH) analysis, not only inflammatory cells in tumor stroma but also tumor cells showed positive signals for OPN mRNA. By immunohistochemistry, co-immunoreaction of OPN and CD44v9 in tumor cells obviously correlated with the degree of lymphatic vessel invasion or long distant lymph node metastases in poorly differentiated gastric cancer. Interestingly, strong co-immunoreaction of OPN and CD44v9 of tumor cells was concommitant with cluster formation in the lymphatic vessels. Our results suggest that overexpression of OPN correlated with the progression of human gastric carcinoma. Especially in CD44-bearing poorly differentiated gastric cancer, interaction between OPN and CD44 may parallel lymphogenous metastasis. Int. J. Cancer (Pred. Oncol.) 79:127–132, 1998.© 1998 Wiley-Liss, Inc.