KL-6 mucin expression in carcinoma of the ampulla of Vater： Association with cancer progression

AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Positive staining of ampullary carcinoma cells was observed in 26 (68.4%) cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis (P=0.020), pancreatic invasion (P=0.016), duodenal invasion (P= 0.034), and advanced stage of TNM clinical classification (P=0.010). Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis (P=0.029). CONCLUSION: The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of carcinoma of the ampulla of Vater.     

整合素β3表达与结直肠癌淋巴结转移的相关性

目的探讨结直肠癌患者肺转移重要的血管内皮细胞标志物整合素β3（ITGB3）表达与结直肠癌转移之间的相关性。 方法采用免疫组织化学染色法检测49例原发性结直肠癌患者癌组织、癌旁正常肠黏膜组织以及相应淋巴结组织中ITGB3的表达。其中37例患者有淋巴结转移。分析ITGB3表达与患者结直肠癌转移的相关性。 结果免疫组化染色结果显示,ITGB3主要在原发性结直肠癌组织、癌旁正常肠黏膜细胞质以及相应淋巴结的间质中表达。ITGB3在不同组织的表达不同,在癌组织中的表达低于癌旁正常肠黏膜组织,且差异有统计学意义（P<0.01）;有淋巴结转移患者淋巴结ITGB3表达高于无淋巴结转移患者,且差异有统计学意义（P<0.001）。淋巴结上皮细胞ITGB3的表达与淋巴结间质组织的表达呈正相关（r=0.395,P=0.005）;且有淋巴结转移患者癌组织上皮细胞ITGB3表达与淋巴结上皮细胞ITGB3表达呈正相关（r=0.514,P=0.001）。ITGB3在淋巴结表达、上皮细胞表达以及间质表达均与淋巴结转移呈正相关（r=0.659,P<0.0001;r=0.661,P<0.0001;r=0.354,P=0.013）。 结论ITGB3淋巴结表达与结直肠癌淋巴结转移呈正相关。ITGB3可能是原发性结直肠癌患者淋巴结转移的潜在分子标志物。     

Sialoglycoconjugate expression in primary colorectal cancer and metastatic lymph node tissues

BACKGROUND/AIMS: Aberrant cell surface glycosylation, and especially excessive sialylation, is thought to have great importance in tumor malignancy. To investigate the clinicopathological significance of sialylation in colorectal cancer, we performed histochemical analyses using sialic acid-binding lectins. METHODOLOGY: Primary colorectal cancer and lymph node tissues obtained from 80 cases were subjected to lectin-immunohistochemical staining using Maackia amurensis leukoagglutinin (MAL) and Sambucus nigra agglutinin (SNA). The relationship between the staining characteristics and the various clinicopathological parameters was statistically analyzed. RESULTS: In primary cancer tissues, a high level of SNA staining was significantly related to worse prognosis and some pathological characteristics such as lymph node metastasis, whereas a high level of MAL staining was related to worse prognosis. In metastatic lymph node tissues, positive staining was frequently found for MAL and SNA, which wasremarkable in cases categorized as N2 metastasis. Furthermore, cases with MAL-positive staining in metastatic lymph node tissues evidently indicated worse prognosis than those with MAL-negative staining. CONCLUSIONS: Aberrant expression of SNA-positive sialoglycoconjugates in primary colorectal cancer tissues is important in terms of unfavorable pathological characteristics of the cancer. In addition, aberrant expression of MAL-positive sialoglycoconjugates in metastatic lymph node tissues might be related to worse prognosis.     

大肠癌组织中生长抑素和血管内皮生长因子-C的表达及其临床意义

目的探讨大肠癌组织中生长抑素（SS）和血管内皮生长因子-C（VEGF-C）的表达及其临床意义。方法采用免疫组化法检测60例大肠癌组织及20例正常大肠黏膜组织中SS蛋白和VEGF-C蛋白的表达，采用VEGF-C受体FLT-4阳性脉管标记淋巴管计数，分析SS与大肠癌淋巴管生成、转移的关系。结果SS蛋白表达阳性率在大肠癌组及正常大肠黏膜组分别为37．7％和65％，VEGF-C在癌及正常组阳性表达率分别为60％和30％，差别均有显著性；SS表达与肿瘤分化程度、淋巴结转移、淋巴管侵犯及远处转移密切相关，与浆面膜受累无关；VEGF-C表达与肿瘤淋巴结转移，淋巴管侵犯及远处转移密切相关，而与肿瘤分化和浆面膜受累无关；大肠癌组织中SS和VEGF-C蛋白表达呈显著负相关。结论SS可能通过对VEGF-C／FLT-4信号通路的阻滞而抑制大肠癌淋巴管生成及转移。     

Immunohistochemical localization of carcinoembryonic antigen as a predictor of lymph node status in submucosa-invasive colorectal carcinoma

PURPOSE: Submucosa-invasive colorectal carcinoma is a colorectal carcinoma extending only into the submucosal layer. To clarify the metastatic potential of submucosa-invasive colorectal carcinoma, we studied the relationship between the immunohistochemical staining pattern of carcinoembryonic antigen (CEA) and that of lymphatic invasion/ lymph node metastasis. METHODS: We investigated 49 submucosa-invasive colorectal carcinomas resected surgically or endoscopically. CEA distribution patterns of the neoplastic tissues were divided into three patterns: Pattern 1 = luminal type; Pattern 2 = apical cytoplasmic type; and Pattern 3 = diffuse cytoplasmic type. We also observed the submucosal stromal staining of CEA. RESULTS: Lymphatic invasion and lymph node metastasis were found in 48.8 percent (21/43) and 11.6 percent (5/43) of the Pattern 2/Pattern 3 cases, whereas these were seen in none (0/6) of Pattern 1 cases. Lymphatic invasion and lymph node metastasis were found in 63.3 percent (19/30) (chi-squared =21.94;P <0.001) and 16.7 percent (5/30) of the positive stromal CEA cases, whereas these were seen in 10.5 percent (2/19) and none (0/14) of the negative stromal CEA cases, respectively. CONCLUSION: Pattern 2/Pattern 3 and stromal CEA can be predictors of the lymph node metastasis with 11.6 percent and 16.7 percent risks.Read at the meeting of the Japanese Society of Gastroenterological Surgery, Tokyo, Japan, February 24 to 25, 1994.     

CCR7和L-选择素在大肠癌组织中的表达及意义

目的探讨CC趋化因子受体7(CCR7)和黏附分子L-选择素在大肠癌组织中的表达及二者与大肠癌淋巴转移的关系。方法采用免疫组织化学方法检测63份大肠癌组织(大肠癌组)、44份癌旁正常组织(癌旁组)和31份转移灶组织(转移组)中CCR7和L-选择素的表达。结果大肠癌组、转移组CCR7、L-选择素阳性率明显高于癌旁组(P<0.01);CCR7与L-选择素表达显著相关(r=0.653,P<0.01);有淋巴结转移者明显高于无转移者,P<0.05。结论 CCR7与L-选择素在大肠癌中的表达与大肠癌的发生和淋巴转移有关,二者可能共同参与了大肠癌发生及淋巴结转移过程;检测二者表达情况有助于判断大肠癌患者的预后。     

survivin和PTEN蛋白在大肠癌中的表达及临床意义

目的探讨生存素(survivin)和磷酸脂酶(PTEN)蛋白表达与大肠癌浸润转移的关系及相关性。方法应用免疫组织化学技术,检测90例大肠癌组织中survivin和PTEN蛋白表达。结果90例大肠癌中survivin和PTEN蛋白阳性表达率分别为65.6%(59/90)和46.7(42/90)。survivin高表达及PTEN低表达与大肠癌Dukes分期、浆膜浸润、淋巴结转移、肝脏转移均呈正相关(P<0.05)。大肠癌中survivin表达与PTEN表达呈负相关(r=-0.50,P<0.05)。结论survivin和PTEN表达与大肠癌浸润转移密切相关。检测survivin和PTEN蛋白表达可作为判断大肠癌预后的客观指标。     

Transforming growth factor—β1in invasion and metastasis in colorectal cancer

AIM：To investigate the role of TGFβ1 in invasion and metastasis in colorectal cancer by analysing TGFβ1 correlated wity depth of tumor invasion,stage and metastasis.METHODS:Serum TGFβ1levels were determined in50patients with colorectal cancer and 30healthy volunteers using a TGFβ1 enzyme-linked immunosorbent assay.TGFβ1 expression in primary and lymph node metastatic lesions were detected in 98cases of colorectal cancer by immunohistochemical staining and in situ hybridization.RESULTS:Serum levels of TGFβ1 in patients with colorectal cancer(40&#177;18μg&#183;L^-1)were significantly higher than those in the healthy control group(19&#177;8μg&#183;L^-1),P&lt;0.05.Elevated levels of serum TGFβ1were found in 60%of patients with colorectal cancer when the mean+2s was used as the upper limit of the normal range(35.1μg&#183;L^-1).Increases in serum TGFβ1 levels were significantly asociated with Dukei‘s stage(P&lt;0.05),but there was no significant difference between,Duki‘s stage Bpatients and Dukei‘s stage Cpatients.In the cytoplasm of cancer cells,TGFβ1 was immunostained in37.8%(37/98)of colorectal cancer,and this expression was confirmed by in situ hybridization,Among35cases of colorectal cancer with lymph node metastatic lesions,TGFβ1 positive staining was found in18(51.4%)cases of primary tumor,and 25(71.4%)cases with lymph node metastatic lesions,respectively,Of17cases with no staining in the primary lesion.7(41.2%)casesshowed TGFβ1 staining in the metastatic lesion.Serum TGFβ1 levels and TGFβ1 expression in colorectal cancer tissues were correlated significantly with depth of tumor invasion,stage and metastasis,Patients in stage C-D,T3-T4and with metastasis had significantly higher TGFβ1 levels than patients in stage A-B,T1-T2and without metastasis(P&lt;0.05).CONCLUSION:These results suggest that transforming growth factor-β1 is closely related to the invasion and metastasis of colorectal cancer.It increased the invasive and metastatic potential of tumor by altering a tumor microenvironment.TGFβ1 may be used as a possible biomarke.     

C-erbB-2蛋白和缝隙连接蛋白43在胃癌组织中的表达及意义

目的探讨C-erbB-2癌蛋白和缝隙连接蛋白43（connexin,Cx43）在腺型胃癌中的表达并分析其临床意义。方法应用免疫组织化学SP法分别检测C-erbB-2癌蛋白、Cx43在48例腺型胃癌和26例胃炎组织中的表达,并分析其与临床病理参数的关系。结果C-erbB-2癌蛋白、Cx43阳性呈棕黄色颗粒定位于细胞膜或细胞质;C-erbB-2癌蛋白在胃癌中的阳性表达率（50.0%）显著高于胃炎黏膜组织的阳性率（2χ=6.70,P〈0.05）;Cx43在胃癌中阳性率（43.8%）显著低于胃炎黏膜组织的阳性率（χ2=23.03,P〈0.05）;C-erbB-2癌蛋白的表达与胃癌的大小、分化程度及淋巴结转移呈显著相关（2χ=6.00、9.41、5.49,P值均〈0.05）;Cx43蛋白表达降低或缺失同样与胃癌的分化程度及淋巴结转移呈显著相关（χ2=7.49、6.86,P值均〈0.05）;C-erbB-2癌蛋白和Cx43蛋白呈负相关（χ2=0.01,r=-0.378,P〈0.05）。结论C-erbB-2癌蛋白的高表达、Cx43表达降低或缺失与胃癌分化程度、浸润转移密切相关,联合检测C-erbB-2和Cx43有助于判断胃癌的生物学行为。     

Expression of the human phosphatases of regenerating liver (PRLs) in colonic adenocarcinoma and its correlation with lymph node metastasis

Background Human phosphatases of regenerating liver (PRLs) can induce cell growth, differentiation, and malignant transformation. In this study, we used specific polyclonal antibodies against PRLs to investigate their expression in colonic adenocarcinomas and its correlation with patient gender, age, tumor differentiation, localization, invasion, and metastasis. Materials and methods The polyclonal antibodies against PRL-1, PRL-2, and PRL-3 were produced and purified. The expression of PRLs in human colorectal carcinoma cell lines (SW480 and SW620) was examined by Western blotting. We also examined their expression in normal and pathologic tissues from the human colon. The tissues included 49 primary colonic adenocarcinomas, 14 cases with lymph node metastases, 15 colonic adenomas, and 12 normal colon samples. Hematoxylin and eosin staining, immunohistochemistry, and semiquantitative morphological analysis were used to evaluate the sections. Results PRLs were widely expressed in SW480 and SW620. PRL-1, PRL-2, and PRL-3 were expressed, respectively, in 16, 10, and 16% of primary colonic adenocarcinomas. In contrast, PRLs were strongly expressed in all lymph node metastases. There were no significant correlations between the expression of PRLs and patient gender, age, tumor differentiation, depth of invasion, or localization of tumor within the different sections of the colon. PRLs were not expressed in normal colon tissues or in colonic adenomas. PRLs were mainly expressed in the cytoplasm and at the cytoplasmic membranes of the colonic adenocarcinoma cells as well as in the endothelial cells and the surrounding smooth muscle cells of larger vessels in the lymph node metastases. Conclusion Colonic adenocarcinoma cells have the ability to produce PRLs, which may relate to the lymph node metastasis of colonic adenocarcinoma. Y. Wang and Z.-F. Li contributed equally to this work.     

巨噬细胞移动抑制因子在大肠癌中的表达及其与细胞凋亡的关系

目的观察巨噬细胞移动抑制因子在大肠癌中的表达及其与细胞凋亡的关系。方法应用免疫组化技术及DNA原位末端标记TUNEL法分别测定43例大肠癌及10例正常大肠组织中的MIF蛋白表达和细胞凋亡。结果大肠癌组织中的MIF表达率为65．1％（28／43），明显高于正常大肠组织0．0％（0／10），二者之间有显著性差异（P〈0．01）。MIF表达与大肠癌组织学类型及Dukes分期无明显相关（P〉0．05），但与大肠癌分化程度、淋巴结转移呈显著相关（P〈0．05）。MIF蛋白的表达与细胞凋亡指数呈负相关（r=-0．436，P〈0．01）。结论MIF蛋白的异常表达而引起的细胞凋亡抑制或逃避，在大肠癌的发生、发展中起一定的作用。联合检测MIF蛋白和凋亡指数，有助于对肿瘤细胞的分化程度作出正确评价，以指导临床治疗及估计预后。     

Ezrin、FAK及E-cadherin在大肠癌组织中的表达及其临床意义

目的:探讨大肠癌组织中埃兹蛋白(Ezrin),黏着斑激酶(FAK)及上皮细胞钙黏蛋白(E-cadherin)的表达及其与肿瘤侵袭和转移的关系.方法:大肠癌组织标本50例,其中高分化腺癌13例,中低分化腺癌37例;无淋巴结转移30例,淋巴结转移20例.采用免疫组织化学方法检测50例大肠癌组织中Ezrin,FAK及E-cadherin的蛋白表达,并运用统计学方法分析Ezrin,FAK及E-cadherin的表达与大肠癌各种临床病理特征的关系及三者的相关性.结果:Ezrin在中低分化、伴有淋巴结转移及Dukes C D期大肠癌的阳性表达率显著高于高分化、无淋巴结转移及Dukes A B期大肠癌(83.78% vs 46.15%,P<0.01;95.00%vs 60.00%,P<0.01;95.00% vs 60.00%,P<0.01),而E-cadherin在以上组织中的表达正好相反(24.32% vs 69.23%,P<0.01;10.00% vs 53.33%,P<0.01;10.00% vs 53.33%,P<0.01),其均与患者性别及年龄大小均无关(P>0.05).FAK在Dukes C D期、伴有淋巴结转移大肠癌组织中的阳性表达显著高于Dukes A B、无淋巴转移组织(100.00% vs 63.33%,P<0.01;100.00% vs 63-33%,P<0.01),而与肿瘤的分化程度、患者性别及年龄大小均无关(P>0.05).经Spearman相关分析,Ezrin与FAK在大肠癌组织中的表达呈正相关(r=0.346,P<0.05),E-cadherin与Ezrin、FAK在大肠癌组织中的表达均呈明显负相关(r=-0.410,P<0.01;r=-0.406,P<0.01).结论:Ezrin,FAK及E-cadherin在大肠癌组织中的异常表达与肿瘤组织的浸润和转移密切相关,联合检测可以作为一组有效的大肠癌肿瘤标记和预后指标.     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.     

KL-6-producing invasive thymoma

We report a patient with KL-6-producing invasive thymoma. A 58-year-old man was admitted complaining of dyspnea and fatigability. Computed tomography of the chest revealed interstitial pneumonia and an anterior mediastinal tumor. The tumor was surgically extirpated and diagnosed as invasive thymoma. Serum KL-6 levels later increased further and another tumor was found in the liver. That liver tumor was resected and histologically diagnosed as a metastasis of thymoma. Following resection, the serum KL-6 level decreased. Tumor cells of both primary and metastatic lesions exhibited positive reactivity to immunohistochemical staining for KL-6. A review of this case is presented.     

Evaluation of Tumor Cell Dissociation as a Predictive Marker of Lymph Node Metastasis in Submucosal Invasive Colorectal Carcinoma

PURPOSE Tumor cell dissociation—the histologic finding of small solid carcinoma cell clusters and groups of dissociated dedifferentiated carcinoma cells at the invasive front–is related to tumor metastasis and patient prognosis. However, few previous reports have examined tumor cell dissociation in submucosal invasive colorectal carcinoma. We investigated the relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. We also examined immunohistochemical expression of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma.METHODS Submucosal invasive colorectal carcinoma tissue samples from 20 patients with lymph node metastasis and 100 patients without lymph node metastasis were evaluated. Sections stained with hematoxylin and eosin were evaluated for tumor cell dissociation. Immunohistochemistry was used to determine the expression and cellular distribution of E-cadherin and beta-catenin.RESULTS Tumor cell dissociation was more frequently identified in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.0001). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with lymph node metastasis than in those without lymph node metastasis (P = 0.025). Nuclear expression of beta-catenin tended to be present in submucosal invasive colorectal carcinoma cases with lymph node metastasis (P = 0.063). Decreased membranous expression of E-cadherin occurred more frequently in submucosal invasive colorectal carcinoma cases with tumor cell dissociation than in those without tumor cell dissociation (P = 0.0023).CONCLUSIONS Our results suggest that there is a relation between tumor cell dissociation and lymph node metastasis in submucosal invasive colorectal carcinoma. Tumor cell dissociation formation might be related to abnormal expression patterns of E-cadherin and beta-catenin in submucosal invasive colorectal carcinoma. Tumor cell dissociation and decreased membranous expression of E-cadherin would be important predictive markers for lymph node metastasis in submucosal invasive colorectal carcinoma.Presented at the 93rd Japanese Society of Pathology, Sapporo, Japan, June 9 to 11, 2004.     

Expression of insulin-like growth factor-2, c-MET, matrix metalloproteinase-7 and MUC-1 in primary lesions and lymph node metastatic lesions of gastric cancer

BACKGROUND/AIMS: Lymph node metastases are thought to be formed as lymphatic flow, so the first metastasis is formed in the lymph node nearest the primary tumor and then further lymph node metastases are formed continuously down stream. In this study of gastric cancer, we evaluated whether IGF-2 (insulin-like growth factor-2), c-MET (hepatocyte growth factor receptor), MMP-7 (matrix metalloproteinase-7) and MUC-1, which are associated with nodal metastasis from primary tumor, are concerned with metastasis from nodal metastatic lesion to other nodes. METHODOLOGY: Tissue specimens were obtained from 146 patients who underwent gastrectomy at the Department of Surgery II of Kanazawa University between 1989 and 1997. We evaluated the expression of IGF-2, c-MET, MMP-7 and MUC-1 in 146 primary tumors and 66 metastatic lymph nodes by immunohistological staining. RESULTS: In primary lesions, these 4 factors had significant association with lymphatic vessel infiltration and MMP-7 and MUC-1 had significant association with nodal metastases. In nodal metastatic lesions, positive rates of MMP-7 and MUC-1 were higher than in primary lesions. Furthermore, 37 (73%) of the 51 cases with positive staining for MMP-7 in metastatic lesions in perigastric lymph nodes and 5 (33%) of the 15 cases without the staining had nodal metastases in group 2 or more, showing significant difference (P < 0.05). And 37 (76%) of the 49 cases with positive staining for MUC-1 in metastatic lesions in perigastric lymph nodes and 5 (29%) of the 17 cases without the staining had nodal metastases in group 2 or more, showing significant difference (P < 0.01). CONCLUSIONS: MMP-7 and MUC-1 were associated with not only nodal metastasis from primary tumor but also metastasis from nodal metastatic lesion to other nodes.     

Expressions of p53, VEGF C,p21: could they be used in preoperative evaluation of lymph node metastasis of esophageal squamous cell carcinoma?

The prognosis of esophageal squamous cell carcinoma is primarily determined by staging. Although radiological methods have revealed lymph node metastasis preoperatively, these radiological findings cannot be correlated with pathological staging. The aim of this study was to compare the expressions of p53, vascular endothelial growth factor C (VEGF C) and p21 with lymph node metastasis in preoperative endoscopic biopsy and postoperative resection material. Tissue samples were taken from 40 patients who had undergone endoscopic biopsies and radical esophagectomies. The expressions of p53, VEGF C and p21 proteins in these sections were immunohistochemically examined. The expression of each antibody was characterized as a negative or positive reaction according to the pattern and intensity of semiquantitative immunostaining. The staining pattern of antibodies was divided into three groups: < 10% cancer cells were accepted to be (-), 10-50% were (+), heterogenous and > 50% were (+ +), homogenous. For each antibody, statistical correlation with conventional prognostic parameters such as localization, microscopic grade, stage, pathological lymph node metastasis and survival, were investigated. p53 expression was observed in 65.5% (19/29) of lymph node positive cases, whereas p53 was in 50% (20/40) of cases. VEGF C was in 65% (26/40) and p21 was in 15% (6/40) of cases. p53 has the specificity of 90.9% and sensitivity rate of 65.5% in detecting lymph node metastasis and positive predictive value was 95%. Expression of p53 was significantly correlated with stage and lymph node metastasis (P = 0.02 and P = 0.03, respectively). Prediction of lymph node metastasis by p53 was correlated independently and in coexpression with VEGF C (P < 0.01). There was no relation detected between p21 and other parameters. In esophageal squamous cell carcinoma (SCC), p53 and VEGF C expressions were correlated with pathologically positive lymph nodes. When preoperative staging has been insufficient in esophageal carcinoma cases, immunohistochemical analysis of p53 and VEGF C staining in tissues could be an aid to clinicians regarding lymph node metastasis.     

RUNX3蛋白在人结直肠癌中的表达及其临床意义

背景:Runx3(runt相关转录因子3)基因是一种新发现的抑癌基因,近年研究发现Runx3异常表达与人类多种消化系肿瘤的发生密切相关。目的:研究人结直肠癌中RUNX3蛋白的表达,分析其表达与结直肠癌临床病理特征的关系。方法:以免疫组化方法检测90例结直肠癌患者的癌组织和癌旁组织中RUNX3蛋白的表达。结果:结直肠癌组织中RUNX3蛋白的阳性表达率(47.8%,43/90)显著低于癌旁结直肠黏膜组织(100%,P<0.05)。RUNX3蛋白的表达与结直肠癌患者的性别、年龄、肿瘤部位、大小和组织学类型无关(P>0.05),与肿瘤浸润深度、分化程度、Dukes分期和有无淋巴结转移有关(P<0.05),浸润越深、分化程度越低、Dukes分期越晚和有淋巴结转移的癌组织,RUNX3蛋白低表达越明显。结论:RUNX3蛋白的表达可能与结直肠癌的浸润、分化和转移相关,提示RUNX3蛋白表达下调可能对结直肠癌的发生、发展具有重要作用。     

Matrix metalloproteinase-2 and tissue inhibitor of metallo-proteinase-2 in colorectal carcinoma invasion and metastasis

AIM: To explore the relationship between matrix metallopr- oteinase-2 (MMP-2) and tissue inhibitor of metallopr- oteinase-2 (TIMP-2) in the development of colorectal carcinoma and to provide a valuable marker for clinical diagnosis. METHODS: Twenty-five patients with colorectal carcinoma underwent surgical resection. Samples were taken from tumor sites and normal tissues. MMP-2 activity was determined by gelatin zymography. Western blot and ABC immunohist-ochemical staining were used to detect the expression levels of MMP-2 and TIMP-2 in normal and colorectal carcinoma tissues. Statistical analyses were performed using the Student's t test and one-way ANOVA. P<0.05 was considered statistically .significant. All the statistical analyses were performed using SPSS 10.0 software. RESULTS: MMP-2 activity could be detected in both normal and colorectal carcinoma tissues. MMP-2 activity in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t=3.916,4.227). MMP-2 activity was positively related to the colorectal carcinoma invasion depth, lymph node metastasis and Duke's stage. Western blot and ABC immunohistochemical staining demonstrated that the expression level of MMP-2 in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t = 9.429), but the expression level of TIMP-2 in colorectal carcinoma tissues was much lower than that in normal tissues (P<0.05, t = 7.329). The MMP-2/TIMP-2 ratio of colorectal carcinoma was much higher than that of normal tissues. With the progression of invasion depth, lymph node metastasis and tumor Duke's stage, the activity and expression level of MMP-2 and TIMP-2 gradually increased, but the MMP-2/TIMP-2 ratio gradually decreased. CONCLUSION: The balance between MMP-2 and TIMP-2 plays a crucial role in the process of colorectal carcinoma invasion and metastasis.