Expression of c-erbB-2 protein and vessel invasion in colorectal cancer]

Using sections of formalin-fixed, paraffin-embedded tissues from 64 colorectal cancer patients, the expression of c-erbB-2 oncoprotein was studied immunohistochemically. Twenty-seven percent of the cases with liver metastasis showed positive staining. On the other hand, only 3% of cases without liver metastasis were positive. Expression rates of c-erbB-2 protein in liver metastasis cases showed no significant difference between primary operation (26%) and recurrence (27%). Of all c-erbB-2 positive patients, 90% (9/10) had liver metastasis. Secondly, vessel invasions of 45 rectal cancer patients were studied using Victoria Blue (VB) elastic staining and endothelial staining by factor VIII-related antigen and Ulex europaeus agglutinin I (UEA-I) lectin. VB-HE double stain was efficacious to detect vascular invasion, but endothelial staining was not. There were statistically more vascular invasions in 30 patients with liver or lymph node metastases than in those without metastasis. And in cases with metastasis, many vascular invasions into the extra-muscular layer were seen. Both vascular invasions and c-erbB-2 protein were valuable indicators of possible liver metastasis.     

Expression of CD44 Variant Exons 8–10 in Colorectal Cancer and Its Relationship to Metastasis

Splice variants of CD44 are overexpressed in human lung, breast, and colon carcinoma cell lines. This study was conducted to clarify the association between the expression of CD44 variant exons 8–10 and metastatic potential in human colorectal cancer. We found that the expression of a CD44 splice variant containing exons v8–10 was increased in all of 60 colorectal cancer specimens examined compared with matched normal colorectal mucosa, as determined by Northern blotting. Expression of CD44 variant exons 8–10 did not significantly correlate with histological type, depth of tumor invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the level of CD44 variant exon 8–10 expression was significantly higher in carcinomas associated with liver metastasis than in those without liver metastasis. In addition, expression of CD44 variant exons 8–10 in the liver metastases was more intense than that in the primary colorectal cancers. These findings indicated that this domain of the CD44 glycoprotein encoded by exons v8–10 may play an important role in tumor hematogenous metastasis of human colorectal cancer.     

Study of c-erbB-2 protein and epidermal growth factor receptor expression and DNA ploidy pattern in colorectal carcinoma

Correlation of c-erbB-2 protein (n = 44), epidermal growth factor receptor (EGFR) (n = 41) expression, and DNA ploidy pattern (n = 42) with clinical outcomes of human colorectal cancers was studied. Using monoclonal antibodies against c-erbB-2 protein and EGFR, an immunohis-tochemical study of the expression of c-erbB-2 protein and EGFR in frozen tissue sections from the lesion was performed. There was no significant correlation between the expression of c-erbB-2 protein and clinicopatho-logical findings such as, tumor size, histological type, depth of invasion, lymph node metastasis, lymphatic vessel invasion, or venous invasion. However, the incidence of c-erbB-2 protein expression in Dukes D was significantly higher (9/10, 90%) than that in Dukes A to C (16/34, 47.1%). Similar tendency was also observed in the expression of EGFR. Aneuploid case was observed in 12 of observed 25 (48%) cases without lymph node metastasis, while it was observed in 16 of 17 cases (94.1%) with lymph node metastasis and there was significant association between DNA ploidy pattern and lymph node metastasis (P< 0.01) and most of the cases (17/20, 85%) were aneuploidy in Dukes C and D. The results above suggest that the expression of c-erbB-2 protein or EGFR was associated with distant metastasis, while on the other hand DNA ploidy pattern was correlated with lymph node metastasis. © 1993 Wiley-Liss, Inc.     

Expression of EphA2 and E-cadherin in colorectal cancer: correlation with cancer metastasis

Recently, overexpression of EphA2, a member of the Eph family of receptor tyrosine kinases, has been reported in several cancers. Reduced expression of E-cadherin, an intercellular adhesion molecule of epithelial cells, has been reported to be associated with aggressive clinicopathological phenotypes in various cancers. In epithelial cells, EphA2 and E-cadherin co-localize to sites of cell-cell contact, and it has been shown that E-cadherin regulates EphA2. This study aimed to clarify the relationship between the expression of the EphA2 and E-cadherin proteins and clinicopathological characteristics, with reference to the expression levels of both EphA2 and E-cadherin, in patients with colorectal cancer. We performed immunohistochemical staining of EphA2 and E-cadherin with EphA2 and E-cadherin monoclonal antibodies in samples from 194 primary lesions of colorectal cancer. The expression level of EphA2 had a statistically significant relationship with liver metastasis, lymphatic vessel invasion and clinical stage (p=0.0477, 0.0316 and 0.0467, respectively). In addition, the positivity rate of EphA2 was significantly higher in primary lesions with lymph node metastasis than in those without metastasis (p=0.0014). However, the expression level of E-cadherin had an inverse relationship with both differentiation level of the tumor and lymphatic vessel invasion (p=0.0430 and 0.0320, respectively). Furthermore, a significant relationship between the expression of EphA2 and E-cadherin was observed. In conclusion, our study revealed that the overexpression of EphA2 protein in colorectal carcinoma tissue correlates closely with cancer progression and hematogenous and lymphogenous metastasis, suggesting that both EphA2 and E-cadherin may play an important role in tumor metastasis in colorectal cancer.     

血管内皮生长因子、癌基因c-erbB-2在胃癌中的表达及临床意义

目的：探讨血管内皮生长因子（VEGF）、癌基因c-erbB-2在胃癌组织中表达及其临床特征之间的关系。方法：应用免疫组化技术，检测102例人胃癌组织中VEGF、c-erbB-2蛋白表达，分析VEGF、c-erbB-2与胃癌组织学分型、浸润深度、生长方式、淋巴结转移和预后的关系。结果：102例胃癌组织中VEGF表达阳性率为50％（51／102）与胃癌浸润深度（P＜0．01）、生长方式（P＜0．01）、淋巴结转移（P＜0．01）密切相关，而与组织学类型无关（P＞0．05）。102例胃癌组织中c-erbB-2表达阳性率为38．24％（39／102），与胃癌浸润深度（P＜0．05）、淋巴结转移（P＜0．05）密切相关，而与组织学类型及生长方式无关（P＞0．05）。生存期分析显示VEGF和c-erbB-2阳性的胃癌患者预后差，VEGF表达阳性的或c-erbB2-表达阳性的胃癌患者5年生存率较低。结论：VEGF、c-erbB-2与胃癌的生长、浸润、转移、预后均有密切关系，同时进行VEGF和c-erbB-2免疫组化检测对于评估胃癌的预后会更有意义。     

c-erbB-2,nm23蛋白在结直肠癌组织中的表达及其意义

目的　探讨癌基因c erbB 2及转移抑制基因nm 2 3 ,在结直肠癌组织中的表达及其与淋巴结转移的关系。方法　采用免疫组化S -P法检测 5 9例原发性结直肠癌组织中c erbB 2及nm 2 3基因蛋白的表达。结果　c erbB 2蛋白的阳性表达率 ,在原发性结直肠癌与良性增生性息肉之间有显著性差异 (P <0 .0 5 ) ,阳性表达率与结直肠癌组织分化程度无明显相关 (P >0 .0 5 ) ,与淋巴结的转移呈正相关 (P <0 .0 5 )。nm 2 3蛋白在结直肠癌淋巴结无转移组中显著高于有转移组 (P <0 .0 5 ) ,与结直肠癌淋巴结转移呈负相关。结论　c erbB 2及nm 2 3异常表达在结直肠癌发生发展和淋巴结转移中起重要作用 ,联合检测c erbB 2及nm 2 3蛋白 ,对判断结直肠癌患者预后和淋巴结转移有一定的参考价值     

贲门癌中c-erbB-2、MTA1及E-cadherin的表达

 目的探讨c-erbB-2、MTA1及E-cadherin蛋白在贲门癌组织中的表达与肿瘤生物学行为的相关性,以及它们三者之间的相关性。方法采用免疫组织化学方法对60例贲门癌组织和18例癌旁组织中c-erbB-2、MTA1及E-cadherin蛋白的表达情况进行检测。结果c-erbB-2的表达与贲门癌的浸润、转移呈正相关,与分化程度呈负相关(P<0.05)。MTA1的表达与贲门癌的浸润深度无显著相关性,与贲门癌的淋巴结转移呈正相关,与分化程度呈负相关(P<0.05)。E-cadherin的表达与贲门癌的浸润深度、转移呈负相关(P<0.05),与分化程度无关。Spearman等级相关分析显示,c-erbB-2与MTA1的表达呈显著正相关(rs=0.276,P<0.05),MTA1与E-cadherin的表达呈负相关(rs=-0.293,P<0.05)。结论c-erbB-2与MTA1的高表达及E-cadherin的表达减少可能是促进贲门癌浸润和转移的重要因素。     

结直肠癌术后肝转移相关因素分析

背景与目的：结直肠癌肝转移作为最常见的转移途径之一，尚缺乏有效的预测、评估指标，本文即探讨结直肠癌术后肝转移与其临床病理因素的关系。方法：比较术后2年发生肝转移107例Dukes B或C期结直肠癌患者与术后2年无肝转移100例患者的血清CEA水平、分析病理切片分化级别、转移淋巴结、淋巴管侵袭以及静脉侵袭的情况。结果：发生肝转移患者远距离淋巴结转移、淋巴管侵袭及镜下静脉侵袭发生率升高，术后CEA持续升高，与无肝转移组比较有显著性差异（P〈0．05）。结论：结直肠癌术中未发现肝转移但有远距离淋巴结转移、淋巴管侵袭或镜下静脉侵袭以及术后CEA持续升高，预示发生肝转移的危险性增加。     

Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis.

The expression of nm23-H1 mRNA and protein was studied in colorectal cancers by Northern blotting and immunohistochemistry. All 21 colorectal cancers studied by Northern blotting had increased levels of nm23-H1 mRNA relative to the adjacent normal colonic mucosa. Increased nm23-H1 protein expression was also observed in all 36 colorectal cancer cases including those studied by Northern blotting. There was no significant correlation between nm23-H1 expression and tumour histology, serosal invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the expression of both mRNA and protein was significantly lower in tumours associated with liver metastasis than in those without such metastasis. These observations indicate that the nm23 gene may play a role in the suppression of liver metastasis of colorectal cancer.     

c-erbB-2 is not a major factor in the development of colorectal cancer

We have investigated c-erbB-2 protein expression in a large cohort of well-characterized colorectal tumours, and in a subset of lymph node metastases. We have also evaluated a Val(655)Ile single nucleotide polymorphism, which is associated with an increased risk of breast cancer, in a subset of the colorectal cancer patients and in healthy control subjects. Immunohistochemical studies revealed that while 81.8% of tumours expressed c-erbB-2, in the majority of cases equivalent levels of c-erb-B2 were seen in adjacent normal mucosa. Colon tumours were significantly more likely to express c-erbB-2 than rectal tumours (P=0.015). Only 52.4% of the metastases displayed staining patterns concordant with their primary tumour, indicating that determination of c-erbB-2 protein in colorectal tumours cannot predict the status of lymph node metastases. PCR--RFLP analysis of the Val(655)Ile single nucleotide polymorphism demonstrated that allele frequencies were identical between colorectal cancer patients and a control group of Caucasian subjects (Ile=0.80 and Val=0.20 in each case), indicating that it is not related to the risk of developing colorectal cancer in this population. Furthermore, there was no relationship between c-erbB-2 protein expression and gene polymorphism (P=0.58). In terms of prognosis, no association was seen between either c-erbB-2 protein expression or the presence of the Val allele and patient survival (P>0.05 in each case), suggesting that c-erbB-2 is not a prognostic marker in colorectal cancer.     

Correlation between liver metastasis of the colocalization of actin-related protein 2 and 3 complex and WAVE2 in colorectal carcinoma

Directed movement of normal cells occurs when actin-related protein 2 and 3 complex (Arp2/3 complex) triggers the actin polymerization that forms lamellipodia immediately after binding to WAVE2. In order to determine whether the same mechanism correlates with liver metastasis from colorectal cancer, paired mirror sections of 154 cancer specimens (29 cases with liver metastasis and 125 cases without liver metastasis in which T factor, gender, primary tumor site, and age at operation were matched) were examined immunohistochemically for the localization of Arp2 and WAVE2. Expression of both Arp2 and WAVE2 was detected in the same cancer cells in 55 (35.7%) of the 154 cases, but not detected in the normal colonic epithelial cells. Univariate analysis showed that the colocalization was significantly predictive of liver metastasis (risk ratio [RR] 8.760. Likewise, histological grade (RR 2.46), lymphatic invasion (RR 9.95), and tumor budding (RR 4.00) were significant predictors. Among these, colocalization and lymphatic invasion were shown to be independent risk factors by multivariate analysis. Another 59 colorectal specimens were examined for mRNA expression of Arp2 by real time polymerase chain reaction. High mRNA levels of Arp2, that in situ hybridization revealed to be expressed by the cancer cells, were significantly associated with liver metastasis. However, its effect was absorbed by the influence of risk of the colocalization that is closely related to high expression of Arp2. These results indicate that the colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma.     

Prognostic significance of intrahepatic lymphatic invasion in patients with hepatic resection due to metastases from colorectal carcinoma

BACKGROUND: Intrahepatic spread from liver metastases of colorectal carcinoma has been well described; however, its prognostic value after hepatectomy is controversial. To clearly determine factors predicting survival after hepatectomy in such patients, the authors evaluated 14 clinicopathologic factors of liver metastasis from colorectal carcinoma with special reference to intrahepatic lymphatic invasion. METHODS: The authors retrospectively analyzed data obtained from 67 consecutive patients who underwent hepatectomy for liver metastasis from colorectal carcinoma. Intrahepatic spread was classified into discreet categories that were evaluated separately: invasion to the portal vein, hepatic vein, bile duct, and lymphatic or perineural space. Overall survival and disease free survival periods were examined as functions of clinicopathologic determinants by univariate and multivariate analyses. RESULTS: Intrahepatic spread was found in a total of 28 (43.1%) of the 65 evaluable cases. Portal vein invasion was found in 15 (23.1%) of these cases, hepatic vein invasion in 3 (4.6%), bile duct invasion in 10 (15.4%), and intrahepatic lymphatic invasion in 10 (15.4%). Five year overall and disease free survival rates after hepatectomy were 33.4% and 28.5%, respectively. A short interval (< 12 months) from treatment of primary colorectal carcinoma to liver metastasis and the presence of intrahepatic lymphatic invasion significantly and adversely affected the overall and disease free survival rates. CONCLUSIONS: Intrahepatic lymphatic invasion was shown statistically to be an independent predictor of recurrence and death after hepatectomy in patients with liver metastases from primary colorectal carcinoma.     

CD10蛋白在结直肠癌组织中的表达及其临床意义

目的：研究CD10蛋白在结直肠癌组织中的表达及其与结直肠癌的各临床病理指标之间的关系，探讨其在结直肠癌发生、发展中的作用。方法：收集78例结直肠癌组织标本及22例癌旁正常组织样本，运用免疫组化EliVision法检测CD10蛋白的表达，并采用卡方检验分析其表达强度及分布比例与结直肠癌临床病理指标的关系。结果：CD10蛋白在结直肠癌组织和正常结肠黏膜组织中的阳性表达率分别为46.2%（36/78）和0，差异有统计学意义（P < 0.01）。结直肠癌组织中CD10蛋白表达比例与各临床病理指标均无明显相关（P > 0.05）。结直肠癌组织中CD10蛋白表达强度与患者性别、年龄、肿瘤部位、分化程度、浸润深度无明显相关（P > 0.05），而与肿瘤的临床分期、有无脉管侵犯及淋巴结转移有关（P < 0.05），中晚期结直肠癌CD10蛋白表达强度高于早期肿瘤（P=0.033），周围淋巴结转移阳性的结直肠癌CD10蛋白表达强度高于淋巴结阴性病例（P=0.023），存在脉管受侵犯的结直肠癌CD10蛋白表达强度高于无脉管受侵病例（P=0.004）。结论：CD10蛋白在结直肠癌组织中呈高表达，且表达强度与肿瘤的临床分期、有无脉管侵犯及淋巴结转移有关，可能有促进结直肠癌发展和浸润转移的作用。     

CD10蛋白在结直肠癌组织中的表达及其临床意义

目的：研究CD10蛋白在结直肠癌组织中的表达及其与结直肠癌的各临床病理指标之间的关系,探讨其在结直肠癌发生、发展中的作用。方法：收集78例结直肠癌组织标本及22例癌旁正常组织样本,运用免疫组化EliVision法检测CD10蛋白的表达,并采用卡方检验分析其表达强度及分布比例与结直肠癌临床病理指标的关系。结果：CD10蛋白在结直肠癌组织和正常结肠黏膜组织中的阳性表达率分别为46.2%（36/78）和0,差异有统计学意义（P < 0.01）。结直肠癌组织中CD10蛋白表达比例与各临床病理指标均无明显相关（P > 0.05）。结直肠癌组织中CD10蛋白表达强度与患者性别、年龄、肿瘤部位、分化程度、浸润深度无明显相关（P > 0.05）,而与肿瘤的临床分期、有无脉管侵犯及淋巴结转移有关（P < 0.05）,中晚期结直肠癌CD10蛋白表达强度高于早期肿瘤（P=0.033）,周围淋巴结转移阳性的结直肠癌CD10蛋白表达强度高于淋巴结阴性病例（P=0.023）,存在脉管受侵犯的结直肠癌CD10蛋白表达强度高于无脉管受侵病例（P=0.004）。结论：CD10蛋白在结直肠癌组织中呈高表达,且表达强度与肿瘤的临床分期、有无脉管侵犯及淋巴结转移有关,可能有促进结直肠癌发展和浸润转移的作用。     

THE EXPRESSION OF CATHEPSIN－D，C－erbB－2 AND EGFR IN BREAST CANCER AND ITS CORRELATION TO LYMPHATIC ME

ＴＨＥＥＸＰＲＥＳＳＩＯＮＯＦＣＡＴＨＥＰＳＩＮ－Ｄ，Ｃ－ｅｒｂＢ－２ＡＮＤＥＧＦＲＩＮ　ＢＲＥＡＳＴＣＡＮＣＥＲＡＮＤＩＴＳＣＯＲＲＥＬＡＴＩＯＮＴＯＬＹＭＰＨＡＴＩＣＭＥＴＡＳＴＡＳＩＳＸｕＬｉａｎｇｚｈｏｎｇ许良中；ＺｈｕＷｅｉｐｉｎｇ朱伟萍；...     

300例结直肠癌肝转移患者的临床预后分析

目的 探讨结直肠癌肝转移患者的临床特征及预后因素.方法 对300例结直肠癌首发肝转移患者的临床特征及肝转移后的生存情况进行回顾性分析.结果 300例患者中,原发病灶位于结肠者152例,位于直肠者148例.原发肿瘤为管状腺癌272例,黏液腺癌18例,类癌5例,印戒细胞癌4例,鳞癌1例.原发肿瘤为高分化19例,中分化217例,低分化27例.无区域淋巴结转移104例,有区域淋巴结转移162例.原发肿瘤分期为Ⅰ、Ⅱ期62例,Ⅲ、Ⅳ期为237例.同时性肝转移206例,异时性肝转移94例.肝转移灶为单发48例,多发252例.肝转移灶最大直经≤5 cm249例,>5 cm 51例.300例患者转移后中位生存期为19.0个月,肝转移后1、2和5年生存率分别为79.0%、29.0%和3.0%.单因素分析结果显示,患者KPS评分、组织学分级、原发肿瘤T分期、有无区域淋巴结转移、原发肿瘤分期、有无脉管瘤栓、肝转移灶部位、肝转移灶最大直径、肝转移灶数目、同时合并其他转移均与预后有关.多因素分析结果显示,KPS评分、脉管瘤栓、肝转移灶数目、肝转移灶最大直径是结直肠癌肝转移患者预后的独立影响因素.结论 KPS评分、脉管瘤栓、肝转移灶数目和最大直径是结直肠癌肝转移患者预后的影响因素,KPS评分越高、无脉管瘤栓、肝转移灶数目越少、转移灶最大直径越小的患者预后越好.     

青年结直肠癌c-erbB-2蛋白高表达的病理学意义

目的 :探讨青年结直肠癌c erbB 2表达与临床病理特点之间的联系。方法 :采用流式细胞术对c erbB 2蛋白在青、老年结直肠癌中的表达加以定量检测和对比分析。结果 :青年组 62例中共有 46例c erbB 2阳性表达 ,而老年组 3 2例中有 15例阳性表达 ,二者之间差异有统计学意义 ,P <0 0 5。c erbB 2高表达与青年患者肿瘤组织学类型和浸润深度无明显关系 ,但与肿瘤分级和淋巴结转移密切相关 ,P <0 0 5 ,即分级高或有局部淋巴结转移的多呈高表达 ;反之 ,则几乎均为低表达或无表达。与老年组对比 ,青年组分化程度低、浸润周围软组织或局部淋巴结发生转移的c erbB 2表达量显著升高 ,P <0 0 5。结论 :c erbB 2蛋白的表达对于判断青年结直肠癌恶性程度及预后具有重要病理学意义。     

nm23蛋白与C—erbB—2蛋白在乳腺癌中的表达及临床意义

目的：探讨乳腺癌中抑制转移基因ｎｍ２３的表达及其与Ｃ－ｅｒｂＢ－２、ＥＲ、ＰＲ以及肿瘤组织学分级、淋巴结转移等临床病理特性的相互关系。方法：应用免疫组化ＳＰ法检测７０例乳腺癌中ｎｍ２３蛋白、ＣｅｒｂＢ－２蛋白、ＥＲ、ＰＲ的表达。结果：乳腺癌中ｎｍ２３蛋白阳性率为６２．８６％,ｎｍ２３蛋白的表达与组织学分级、细胞核分级、淋巴结转移以及临床分期均有相关性（Ｐ〈０．０１）,但与Ｃ－ｅｒｂＢ－２蛋白、ＥＲ     

c-MET expression in colorectal adenomas and primary carcinomas with its corresponding metastases

Background

c-MET plays an important role in tumor proliferation, invasion and metastasis. In this study we examined the expression of c-MET in colorectal adenomas, primary adenocarcinomas and their corresponding lymph node, peritoneal and liver metastases. We correlated our findings with clinicopathological features.

Methods

Twenty three cases of colorectal adenoma and 102 cases of primary colorectal carcinoma and their corresponding metastases (44 lymph nodes, 21 peritoneal deposits and 16 liver metastases) were studied to evaluate c-MET expression by immunohistochemistry. For comparison, 12 sections of adjacent healthy colorectal mucosa were examined.

Results

Statistically significant differences were present among normal tissues, colorectal adenomas and primary colorectal carcinomas (P=0.011). Normal tissues showed a negative or weak reaction in 66.67% and 33.33% of cases respectively. Expression of c-MET was positive in 47.8% of adenomas. A significant positive association was identified between c-MET high expression and degree of dysplasia (P=0.024). c-MET was highly expressed in 66.7% of primary colorectal carcinoma. Significant positive correlations were detected between c-MET expression and TNM stage (P=0.036), lymph node metastasis (LNM), peritoneal deposits and liver metastasis (P=0.038, P=0.094 and P=0.045, respectively). c-MET expression in metastatic tissues was significantly higher than that of the primary tumor.

Conclusions

c-MET expression is gradually up-regulated in the development and progression of colorectal cancer (CRC) from normal epithelium to adenoma to colorectal carcinoma to metastases.