Correlation of Skp2 with carcinogenesis, invasion, metastasis, and prognosis in colorectal tumors

In colorectal tumors, S-phase kinase-associated protein 2 (Skp2) still has numerous important questions unanswered: its expression in adenomas, its correlation with key clinicopathological indices, its association with patient prognosis, its variation in lymph node metastases, and its association with many cell-cycle regulators. To answer these questions in colorectal tumors, Skp2, cyclin A, cyclin B1, cyclin E, CDK2, and Ki67 were immunohistochemically stained in 12 normal mucosa, 36 adenomas, 11 carcinomas in adenomas, 102 primary carcinomas, and 12 paired lymph node metastases; and Skp2 was examined by Western blot in 8 pairs of normal mucosa and carcinomas. Situated in nuclei, Skp2 expression significantly increased from normal mucosa through adenoma to primary carcinoma (p<0.0001), from mild through moderate to severe dysplasia in adenomas (p=0.038), from peripheral adenoma to paired central carcinoma (p=0.0033), and from primary carcinoma to lymph node metastasis (p=0.015), and these increases were confirmed by Western blot. Expression, however, relatively declined significantly in the primary carcinomas showing deep invasion (p=0.0113), lymph nodal metastases (p=0.0268), and poor prognosis for all (p=0.0104) or stage III patients (p=0.0119). High Skp2 was also significantly linked with elevated cyclin A, cyclin B1, cyclin E, CDK2 (in primary carcinomas only), and Ki67 in both adenomas and primary carcinomas. Thus, overexpression of Skp2 is associated with colorectal carcinogenesis and late metastasis to lymph nodes, whereas relative reduction of Skp2 is correlated with local invasion of primary carcinoma.     

Nup88 expression in normal mucosa, adenoma, primary adenocarcinoma and lymph node metastasis in the colorectum.

OBJECTIVES: It was the aim of this study to investigate Nup88 expression in normal colorectal mucosa, adenoma, adenocarcinoma and lymph node metastasis, as well as the relationship between Nup88 expression and clinicopathological features. METHODS: Nup88 expression was examined by immunohistochemistry in 84 normal mucosa samples, 32 adenomas, 181 primary adenocarcinomas, and 18 lymph node metastases from colorectal tumour patients. RESULTS: Nup88 expression was observed in normal epithelial and tumour cells. The frequency of strong Nup88 expression was increased from normal mucosa or adenoma to primary tumour and lymph node metastasis (p < 0.0001). There was no significant difference in the expression between normal mucosa and adenoma (p = 0.41). The frequency of strong Nup88 expression was higher in ulcerated tumours (40%) than in polypoid/large fungating tumours (23%; p = 0.048). The frequency of strong Nup88 expression was significantly different among tumours with good (21%), moderate (42%) and poor differentiation (48%; p = 0.01). Nup88 expression was not related to the patients' gender, age, tumour location, size, histological type, invasive depth, lymph node status and Dukes stage (p > 0.05). CONCLUSION: Our results suggest that Nup88 may play a role during the development, aggressiveness and differentiation of colorectal tumours.     

Fatty acid binding protein 6 is overexpressed in colorectal cancer.

PURPOSE: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. Because bile acids are implicated in the carcinogenesis of colorectal cancer, we evaluated FABP6 expression in colorectal cancer. EXPERIMENTAL DESIGN: The expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic lymph nodes. An immunohistochemical study was conducted with paraffin sections. In vitro transfection was done to determine FABP6's biological roles. RESULTS: The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%) than in normal tissue (P<0.001). The expression of mRNA was increased in cancer compared with adenoma, but was dramatically decreased in node metastases. Tumors with high FABP6 expression were smaller in size (P<0.01), more often in the left colon (P<0.05), and had shallower invasion into the bowel wall (P<0.05) compared with those with low expression. There was no significant difference between high- and low-expression tumors regarding clinicopathologic variables such as histologic type, lymph node, or liver metastasis, Dukes' classification, and prognosis. Immunohistochemical study revealed that FABP6 expression was primarily observed in cancer cells. In vitro transfection revealed that transfectants showed weaker invasiveness (P<0.05), more dominant proliferation (P<0.001), and less apoptosis than mock cells. CONCLUSIONS: The expression of FABP6 was higher in primary colorectal cancers and adenomas than in normal epithelium, but was dramatically decreased in lymph node metastases, suggesting that FABP6 may play an important role in early carcinogenesis.     

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.     

Heterogeneous expression and association of beta-catenin, p16 and c-myc in multistage colorectal tumorigenesis and progression detected by tissue microarray

Most colorectal carcinomas (CRCs) arise from adenomas through an archetypal pathogenic pathway, the adenoma-carcinoma-metastasis sequence. Aberrant expression of beta-catenin, p16, E-cadherin and c-myc appears to have played important roles in the development and/or progression of CRC, but their precise distribution pattern and associations in different pathologic loci along CRC's pathogenic pathway have not been thoroughly examined. In this study, a tissue microarray (TMA) containing 85 advanced CRCs in different Dukes stages was constructed. In each of 85 cases, tissue specimens from normal mucosa and primary carcinomas in different layers of the bowel wall were included in the TMA. Tissue specimens from matched adenoma, lymph node metastases and distant metastases were obtained from 22, 21 and 21 cases, respectively. Expression patterns of beta-catenin, p16, E-cadherin and c-myc were evaluated by immunohistochemistry. The results revealed that nuclear expression of beta-catenin, p16 and c-myc was quantitatively increased from normal mucosa to premalignant adenoma, primary carcinoma and lymph node metastatic carcinoma; the frequency of nuclear overexpression of beta-catenin and p16 in lymph node metastases was significantly higher than that in distant metastases (p < 0.05). These results suggest an association between nuclear overexpression of beta-catenin and/or p16 and CRC lymph node metastasis but not distant metastasis. The results also showed that correlative high nuclear expression of beta-catenin and c-myc was observed in primary carcinomas involving the serosa and lymph node metastases (p < 0.05) but not in other pathologic regions of CRCs, suggesting that the tumor microenvironment in different pathologic loci of colorectal tumorigenesis and progression may influence c-myc responsiveness to beta-catenin/Tcf activation.     

nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver.

AIMS: The nm23 gene has been shown to have metastasis suppressing activity and abnormalities of the gene or its expression may be important in tumour progression and dissemination. This study was set out to investigate the possible role of the nm23 in colorectal adenocarcinoma dissemination by examining the level of nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver. METHODS: Using a monoclonal antibody, NCL-nm23 (Novocastra), immunohistochemical expression of the nm23 protein was examined in cases of metastatic colorectal adenocarcinoma in regional lymph nodes (n=71) and liver (n=36). RESULTS: The cases of lymph-node metastasis also had tissues from the primary carcinoma (n=71) and matching normal non-neoplastic mucosal tissues (n=71) from the colon and rectum available for the study. More than half of the cases of primary colorectal carcinoma (43/71; 60%) displayed strong nm23 immunoreactivity, with a similar proportion of the lymph-node metastases (40/71 cases; 56%) having strong nm23 immunostaining. However, only a small minority of the normal controls of non-neoplastic colorectal epithelia (12/71 cases; 17%) had strong nm23 immunoreactivity. The difference in nm23 protein expression between normal colorectal mucosa and primary colorectal carcinoma was statistically significant (P=0.0001; chi-squared test with continuity correction). However, no significant difference in nm23 protein expression was found between primary colorectal carcinoma and lymph-node metastases (P=0.81; chi-squared test with continuity correction). Most of the liver metastases (24/36 cases; 67%) had strong nm23 immunostaining but this finding was not statistically significant when compared with that seen in primary colorectal carcinoma (P=0.62; chi-squared test with continuity correction). In addition, nm23 expression was not found to significantly correlate with 5-year survival of patients with liver metastasis (P=0.86), suggesting that it had no predictive value for overall patient survival. There was also no significant correlation between disease recurrence and nm23 expression (P=0.63). CONCLUSIONS: In summary, increased nm23 protein immunoreactivity is seen in the majority of colorectal carcinomas when compared to normal colorectal tissues but no significant difference in nm23 expression was found between primary colorectal carcinoma and metastatic carcinoma in regional lymph nodes or the liver. This study suggests that increased nm23 expression may be important in early colorectal carcinoma but not in later progression and dissemination of the tumour. In conclusion, the role and importance of the nm23 gene in the development of tumour metastasis in colorectal carcinoma is questionable. Copyright Harcourt Publishers Limited.     

Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival

BACKGROUND: Malignant cells show increased glucose uptake in vitro and in vivo, which is believed to be facilitated by glucose transporters (Gluts). Expression of Glut1, one of the Gluts, has been described in malignancies of the esophagus, colon, pancreas, lung, and brain, but to the authors' knowledge the significance of Glut1 expression in human gastric carcinoma has not been elucidated. The objective of the current study was to examine the expression and distribution of Glut1 and its relation to clinicopathologic parameters in patients with gastric carcinoma. METHODS: Immunohistochemistry with anti-Glut1 antibody was performed on 617 gastric carcinomas and 50 tubular adenomas of the stomach. Glut1-positive and Glut1-negative carcinomas were analyzed for their clinicopathologic characteristics including histologic subtype, depth of invasion, vascular permeation, lymph node and hepatic metastasis, peritoneal dissemination, and prognosis. RESULTS: None of the adenomas expressed Glut1, whereas 182 of 617 carcinomas (29.5%) were positive for the protein. Signet ring cell carcinoma and mucinous adenocarcinoma rarely were positive (2.0% and 6.3%, respectively) and papillary adenocarcinoma (44%) showed slightly higher positivity for Glut1 than tubular (32%) or poorly differentiated adenocarcinoma (28%). Glut1-positive tumor cells were localized mainly in the central part of tumor nests with or without peripheral distribution (92%) but peripheral distribution alone was very limited (8%) (P = 0.0001). Glut1 positivity was associated with depth of invasion (P = 0.0001), lymphatic permeation (P = 0.0001), venous invasion (P = 0.0001), lymph node metastasis (P = 0.0001), hepatic metastasis (P = 0.0001), and carcinoma stage (P = 0.0001). However, peritoneal dissemination was not found to be associated with Glut1 positivity (P = 0.0833). The survival of patients who had tumors that expressed Glut1 was significantly shorter than that of patients with Glut1-negative tumors (P = 0.0001). CONCLUSIONS: In human gastric carcinoma, Glut1 is expressed late in carcinogesis and increases with disease progression. Glut1 expression is associated with tumor aggressiveness and patient survival.     

大肠癌组织Survivin和APRIL表达临床意义探讨

目的探讨大肠癌组织Survivin和APRIL表达的临床意义及其相关性。方法收集常州市第四人民医院2009-08-01-2012-12-31收治且行手术切除大肠癌组织50例、腺瘤组织35例及正常大肠黏膜组织35例,免疫组织化学SP法检测Survivin和APRIL的表达。结果 Survivin和APRIL在大肠癌组织中的阳性表达率分别为76.0%（38/50）和90.0%（45/50）,腺瘤组织中分别为40.0%（14/35）和60.0%（21/35）,均显著高于正常大肠黏膜的0%（0/35）,P〈0.05;Survivin和APRIL在癌组织中阳性表达率也均显著高于腺瘤组织,P〈0.05,呈逐渐升高趋势。有淋巴结转移、浸润浆膜/浆膜外和Dukes C＋D期者的Survivin的表达明显高于无淋巴结转移、浸润深度未穿透浆膜和Dukes A＋B期者,χ^2值分别为5.81、6.17和4.38,P值均〈0.05;组织分级高和有淋巴结转移者的APRIL的表达明显高于组织分级低和无淋巴结转移者,χ^2值分别为5.07和6.34,P值均〈0.05。大肠癌组织中Survivin和APRIL的表达无明显相关性,r=0.105,P〉0.05。结论 Survivin和APRIL在正常大肠黏膜、腺瘤与大肠癌组织表达率逐渐升高,Survivin和APRIL在大肠癌组织表达与病期和分化程度有关,提示与大肠癌发生发展有关;大肠癌组织中Survivin与APRIL表达无明显相关性。     

荧光定量逆转录聚合酶链反应检测大肠癌组织FAK mRNA表达

目的:检测粘着斑激酶(FAK)mRNA在大肠癌及癌旁正常组织中的表达,并探讨其在大肠癌发生、发展中的意义.方法:采用荧光定量逆转录PCR(FQ-RT-PCR)检测30例大肠癌及癌旁正常组织中FAK mRNA的表达.结果:FAK mRNA在大肠癌组织中表达较高,而在癌旁正常组织中表达较低(P=0.011);有淋巴结转移较无转移者FAK mRNA表达高(P=0.021);癌组织浸润程度越深FAK mRNA表达越高(P=0.038).结论:FAK与大肠癌的浸润转移有关,可作为大肠癌发生、发展的预测指标之一.     

DLC-1 expression levels in breast cancer assessed by qRT- PCR are negatively associated with malignancy

Objective: The aim of this study was to explore the expression of DLC-l in breast carcinoma and any associationwith tumor metastasis. Methods: 51 surgical specimens of human breast carcinoma, divided into high invasiveand low invasive groups according to their clinicopathological features, 30 cases of adjacent normal tissue and 28benign breast lesions were examined by qRT-PCR for expression of DLC-1. Results: Expression level of DLC-1 inadjacent normal tissue and benign breast lesion specimens was higher than that in breast carcinoma (P<0.0001);the values in the high invasive group with synchronous metastases were also lower than in the low invasive group(P=0.0275). The correlation between DLC-1 expression level and tumor progression and metastasis of breastcancer was negative. Conclusion: As an anti-oncogene, DLC-1 could play an important part in breast carcinomaoccurrence, progression, invasiveness and metastasis. Detecting the changes of the expression of DLC-1 in thebreast carcinoma may contribute to earlier auxiliary diagnosis of invasiveness, metastasis and recrudescence.     

踝蛋白在大肠癌中的表达及临床意义

目的: 检测踝蛋白(talin)在大肠癌组织中的表达及分布,并探讨其与大肠癌癌变、浸润、转移和分化等临床病理特征之间的关系。 方法: 采用免疫荧光结合激光共聚焦扫描显微镜技术对41例配对大肠正常粘膜组织和原发大肠癌组织,以及19例区域淋巴结转移癌组织中的talin表达水平进行定量检测,并进行统计学分析。 结果: talin蛋白主要位于胞质及胞膜,在正常粘膜组织及癌组织中均有分布。大肠正常粘膜组织中talin的表达水平明显高于大肠原发癌组织,经两相关样本检验,两者表达水平有非常显著性差异(P=0.000)。区域淋巴结转移癌组织与原发大肠癌组织相比较,其talin表达水平更加降低,经两独立样本检验,两者有非常显著性差异(P=0.000);有淋巴结转移的大肠癌组织中talin表达水平明显低于无淋巴结转移的癌组织中talin表达,经两独立样本检验,两者有非常显著性差异(P=0.000);肠壁浸润程度较深的大肠癌组织中talin表达水平明显低于浸润程度较浅的大肠癌组织,经两独立样本检验,两者有非常显著性差异(P=0.002),即talin表达水平与大肠癌浸润肠壁深度呈负相关;talin表达水平与大肠癌分化无相关性,经多独立样本检验,低、中及高分化大肠癌组织中talin表达水平无显著性差异(P=0.153)。 结论: talin与大肠癌的癌变、浸润和转移有关,而与大肠癌的分化程度无明显相关性,talin可作为大肠癌发生、发展的预测指标之一。     

paxillin在大肠癌中的表达及其生物学意义

目的检测桩蛋白(paxillin)在大肠癌组织中的表达,并探讨其在大肠癌发生、发展中的意义。方法采用Western-blot及免疫荧光结合激光共聚焦显微镜对大肠正常黏膜、原发大肠癌及淋巴结转移癌组织的paxillin表达水平进行检测。结果大肠黏膜由良性向恶性转变及转移过程中,paxillin表达水平逐渐升高;有淋巴结转移的大肠癌组织paxillin表达水平明显高于无淋巴结转移者;paxillin表达水平与癌组织浸润肠壁深度呈正相关,而与癌细胞分化程度无明显相关性。结论paxillin与大肠癌的浸润转移有关,可作为大肠癌发生、发展的预测指标之一。     

MDR1和Anxa2在乳腺癌组织中的表达与侵袭转移的关系研究

探讨乳腺癌组织中多药耐药基因（MDR1）和膜联蛋白（Anxa2）表达的相关性及其与乳腺癌转移的关系。方法：应用荧光定量PCR的方法检测20例配对的乳腺导管内癌、100例乳腺浸润性导管癌、70例癌旁正常组织中MDR1和Anxa2 mRNA的相对表达情况。结果：MDR1 mRNA在乳腺导管内癌中的表达水平明显高于癌旁正常组织（P=0.005）,乳腺浸润性导管癌组织中mRNA的表达明显高于癌旁正常组织（P=0.017）和导管内癌（P=0.019 6）。Anxa2 mRNA在乳腺导管内癌中表达与癌旁正常组织相比无显著性差异（P=0.188 9）,但是在乳腺浸润性导管癌组织中的表达明显高于导管内癌（P=0.000 8）和癌旁正常组织（P<0.000 1）;MDR1和Anxa2 mRNA的表达升高均与患者出现淋巴结转移有关（P<0.01）;2种基因在乳腺浸润性导管癌中的表达呈正相关（P<0.000 1）。结论：在肿瘤进展过程中,MDR1和Anxa2 mRNA表达上调与乳腺癌的淋巴结转移有关,二者之间表达具有正相关提示肿瘤细胞的多药耐药的获得和肿瘤侵袭转移之间有着密切联系。     

抑癌基因PTEN在大肠癌癌变过程中表达的实验研究

目的探讨抑癌基因PTEN的表达与大肠癌发生及浸润转移的关系。方法应用免疫组织化学EnVi-sion法原位观察正常大肠粘膜、癌旁单纯增生上皮、增生性息肉、腺瘤型息肉及癌组织中PTEN蛋白的表达。结果正常大肠粘膜均见PTEN蛋白的表达。癌旁单纯增生粘膜、增生性息肉、腺瘤型息肉及癌组织中PTEN蛋白的阳性表达率分别为92.3%、87.5%、70.6%及56.9%,其中早期癌的阳性表达率为66.7%,浸润癌的阳性表达率为55.9%。无淋巴结转移者的阳性表达率为57.5%,有淋巴结转移者为32.0%(P=0.0002)。PTEN蛋白阳性表达率随肿瘤分化程度降低而降低(P=0.028),随肿瘤Dukes分期的增加而下降,但无统计学意义(P>0.05)。结论PTEN蛋白的表达与大肠癌的发生、浸润及淋巴结转移有关,其低表达可能是大肠癌发生的一个信号。     

MMP9及E-cadherin在结直肠癌中的表达及意义

目的:研究基质金属蛋白酶(matrix metalloproteinase-9,MMP 9)、上皮钙黏附素(E-cadherin,E-CD)蛋白在结直肠癌中的表达,探讨其与结直肠癌浸润、转移的关系,以及两者的表达特征和内在联系。方法:应用免疫组化技术SP法检测MMP9和E-cadherin蛋白在52例结直肠癌中的表达情况(其中3例为腺瘤癌变),同时以10例非肿瘤性肠组织作对照。结果:MMP9与淋巴结转移及浸润密切相关。淋巴结转移组(100%)明显高于无淋巴结转移组(89%),生存期<5年的患者组的MMP9过表达显著高于生存期≥5年的患者组(P<0.05)。E-CD表达与有无淋巴结转移相关(P<0.01),与结直肠癌的细胞分化程度、Dukes分期无明显相关性(P>0.05)。结论:MMP9的高表达及E-cadherin失表达或表达减低与结直肠癌转移浸润有密切关系。MMP9的阳性表达与E-cadherin异常表达密切相关。     

Vinculin在大肠癌中的表达及其临床病理意义

目的检测纽蛋白（vinculin）在大肠癌组织中的表达,并探讨其在大肠癌发生、发展中的意义。方法采用免疫荧光结合激光共聚焦显微镜对大肠正常黏膜、原发大肠癌及淋巴结转移癌组织的vinculin表达水平进行检测。结果大肠黏膜由良性向恶性转变及转移过程中,vinculin表达水平逐渐降低;有淋巴结转移的大肠癌组织vinculin表达水平明显低于无淋巴结转移者;vinculin表达水平与癌组织浸润肠壁深度呈负相关,而与癌细胞分化程度无明显相关性。结论vinculin与大肠癌的浸润转移有关,可作为大肠癌发生、发展的预测指标之一。     

Investigation of IL-23 (p19, p40) and IL-23R identifies nuclear expression of IL-23 p19 as a favorable prognostic factor in colorectal cancer: a retrospective multicenter study of 675 patients

IL-23 is a heterodimeric cytokine involved in inflammatory diseases; its role in cancer progression is controversial. Here we analyse the expression of IL-23 subunits (p40 and p19) and IL-23R in colorectal cancer with regard to disease progression, clinical-pathological and molecular aspects. Immunohistochemistry for IL-23p19, IL-23p40, IL-23R and CD8 was performed on a multi-punch tissue microarray of 195 colorectal cancers (cohort 1), matched normal tissue, adenoma and lymph node metastases. Results were compared with clinical-pathological features and CD8+ T-cell counts, then validated on two patient cohorts (cohort 2: n=341, cohort 3: n=139). Cytoplasmic/membranous expression of IL-23 (p19 and p40 subunits) and IL-23R, respectively were over-expressed in carcinomas versus adenomas and normal tissues (p<0.0001) but were reduced in lymph node metastases (p<0.0001). Nuclear IL-23p19 expression was observed in 23.1% and was associated with early TNM stage (p=0.0186), absence of venous (p=0.0124) and lymphatic invasion (p=0.01493), favorable survival (p=0.014) and absence of distant metastasis (p=0.0146; specificity: 100%). This unexpected cellular localization was confirmed by cell fractionation. The beneficial effect of nuclear IL-23p19 was restricted to tumours with CD8+ high counts. Results were validated on Cohorts 2/3. This multicenter study underlines the possible CD8⁺ dependency and beneficial effect of nuclear IL-23p19 on overall patient survival.     

Telomerase activity in colorectal carcinoma and its correlation with expression of c-myc

Objective： To study the role of telomerase activity and c-myc in pathogenesis and progression of colorectal carcinoma, and to investigate the possible regulatory mechanism of telomerase activation. Methods： A modified telomeric repeat amplification protocol （TRAP） and immunohistochemical staining was used to detect telomerase activity and the expression of c-myc in tissue samples from colorectal carcinoma, paracarcinomatousl tissues, normal mucosa, and adenomatoid polyp. Results： The positive rates of telomerase activity and c-myc expression were 83.33% and 80.00% in colorectal carcinoma, 13.33% and 23.33% in paracarcinomatousl tissues, 13.33% and 20.00% in normal mucosa, and 10.00% and 45.00% in adenomatoid polyp respectively, they were significantly higher in colorectal carcinoma than in paracarcinomatousl tissues, normal mucosa, and adenomatoid polyp （P〈0.05）. The rates of telomerase activity and c-myc expression were much higher in colorectal carcinoma with lymph nodes metastases than that without lymph nodes metastases. The expression of c-myc was found being significantly higher in the telomerase positive colorectal carcinoma than in the telomerase negative group （P〈0.05）. Conclusion： The activation of telornerase and abnormal expression of c-myc might play an important role in the process of carcinogenesis and progression of colorectal carcinoma. The over-expression of c-myc may be related to telomerase activation and up-regulation in colorectal carcinoma.     

Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours

EphB2, a receptor tyrosine kinase regulated by the beta-catenin/Tcf4 complex, is expressed in the proliferative compartment of mouse intestine and regulates bidirectional migration of intestinal precursor cells in the crypt-villus axis through repulsive interaction with Ephrin-B ligands. Recently, it has been shown that reduction of EphB activity accelerates colon tumour progression in the Apc(Min/+) mice. In this study, we examined the expression of EphB2 in normal colon, adenomas, primary colorectal cancers (CRCs), lymph node metastases and liver metastases using immunohistochemistry on tissue microarrays. In addition, EphB2 was overexpressed in SW480 colon cancer cells to study its effect in vitro. We found that EphB2 was expressed in 100% of normal colon crypt base cells, 78% of adenomas, 55.4% of primary CRCs, 37.8% of lymph node metastases and 32.9% of liver metastases (all differences were statistically significant at P < 0.001 compared with primary CRCs). Patients with CRCs that lose EphB2 expression had more advanced tumour stage (P = 0.005), poor differentiation (P < 0.001), poor overall survival (P = 0.005) and disease-free survival (P = 0.001), with the latter being independent of tumour stage. In vitro studies showed that overexpression of EphB2 inhibited colon cancer cell growth in colony formation assay and activation of EphB2 receptor inhibited colon cancer cell adhesion and migration. Our data demonstrated a progressive loss of EphB2 expression in each critical step of colon carcinogenesis, including the onset of invasion, dedifferentiation and metastasis which are paralleled by adverse patient outcome. EphB2 may achieve its tumour suppressor function through regulation of cell survival, adhesion and migration.