Reduced E-cadherin expression correlates with increased invasiveness in colorectal carcinoma cell lines

A reduction in cell adhesiveness and cell invasion are essential steps in tumour progression to metastasis. In the present study two out of seven colorectal carcinoma cell lines exhibited reduced expression of the cell-cell adhesion molecule E-cadherin as assessed by immunofluorescence. The same two cell lines were invasive in the collagen gel and membrane invasion culture system invasion assays. Addition of anti-E-cadherin antibody to a non-invasive carcinoma cell line caused the cells to assume a dissociated morphology on plastic and to become invasive in collagen gels. This demonstrates a causal role for E-cadherin in the maintenance of intercellular adhesion and the suppression of tumour cell invasion and possibly metastasis in colorectal tumour cells.     

Increased expression of claudins in cervical squamous intraepithelial neoplasia and invasive carcinoma

Claudins (CLDNs), of which 24 types have been identified, are integral transmembrane proteins of the tight junctions that are critical for maintaining cell adhesion and polarity. They also act as selective barriers. Cells and tissues are characterized by individual CLDN patterns; the composition and levels of expression change during differentiation and tumor formation. Alterations in the expression of individual CLDNs have been detected in several carcinomas and shown to be related to progression and invasion; however, their role in carcinogenesis is controversial. Using a panel of polyclonal (CLDNs 1, 3, and 7) and monoclonal (CLDNs 2 and 4) antibodies, CLDN pattern and expression were studied by immunohistochemistry in 105 cervical tissue specimens, including normal epithelia (n = 20), cervical intraepithelial neoplasias (CINs; CIN 1/2, n = 27; CIN 3, n = 10), carcinoma in situ (CIS, n = 15), and 33 squamous keratinizing and nonkeratinizing invasive carcinomas. No CLDN 3 was observed in normal or intraepithelial neoplastic cells, but significantly increased expression of CLDNs 1, 2, 4, and 7 was detected in the CIN/CIS lesions and invasive carcinomas compared with the normal tissues (P < .001) and reduced reactivity of CLDNs 1 and 2 was observed in invasive cervical cancers compared with CIN 3/CIS (P = .0001) and of CLDNs 2, 4, and 7 compared with CIN 1/2. These results indicate increased expression of CLDNs in the early phase of carcinogenesis in intraepithelial lesions, which decreases during progression to invasive disease. Expression of CLDN 1 was strongest in premalignant stages; thus, it may serve as a good diagnostic marker for the detection of CIN.     

子宫颈上皮内瘤变和子宫颈鳞癌中Twist基因蛋白及Skp2表达

目的 研究Twist和Skp2在子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及子宫颈鳞癌(squamous cell carcinoma,SCC)中的表达及其在癌变中的作用.方法 SP法检测Twist和Skp2在CIN和SCC中的表达,并与正常子宫颈鳞状上皮组对照.结果 正常组、CIN 1级组、CIN 2级组、CIN 3级组及SCC组的Twist和Skp2表达阳性率分别为:0、10%、42.3%、48.3%、52.5%,23.1%、46.5%、73.1%、93.1%和92.5%.Twist和Skp2在正常组与CIN组及SCC组间表达差异有显著性(P<0.005).CIN 1级组与CIN 2级组间表达差异有显著性(P<0.005).结论 Twist和Skp2随着CIN从轻到重至SCC,表达逐渐增强,表明两者在SCC癌变过程中起到协同性作用,共同参与CIN的进展及SCC癌变机制.检测到Twist和Skp2表达增强有助于SCC发生的判断及CIN 1级与CIN 2级分级的临床病理诊断.     

Increased carcinoembryonic antigen expression in cervical intraepithelial neoplasia grade 3 and in cervical squamous cell carcinoma

Carcinoembryonic antigen (CEA) is a highly glycosylated cell surface protein that is overexpressed in a variety of human tumors and has been used as a tumor marker for disease progression in colorectal cancer patients. Recently, CEA has been used as a target for vaccine therapy against advanced CEA-expressing colonic adenocarcinomas. Previous reports have found elevated serum CEA levels in patients with cervical cancer, although this did not correlate with disease progression. In this study, cervical biopsy specimens from patients with normal histology, cervical intraepithelial neoplasia (CIN) grades 1 to 3, cervical squamous cell carcinoma (SCC), and adenocarcinoma were evaluated for CEA expression by immunohistochemistry by using the monoclonal antibody COL-1. Staining intensity was graded on a scale of 0 to 3 and was correlated with histologic diagnoses. CEA staining intensity was significantly increased in high-grade squamous lesions (CIN III and SCC) compared with normal cervical mucosa and CIN grades I or II (P <.0001). There was a linear correlation between grade of lesion and staining intensity (r = 0.71). CEA expression increased most significantly between CIN grades 2 to 3. Only 1 of 7 primary cervical adenocarcinomas expressed CEA. Only 1 of 10 patients with high CEA expression in their tumors by immunohistochemistry had elevated serum CEA. We thus have shown that lesional CEA expression increases in CIN 3 and SCC without elevations in serum CEA. CEA expression may be a useful diagnostic tool and a useful marker for identifying those at risk for progressive cervical neoplasia. HUM PATHOL 31:1357-1362.     

Loss of membranous E-cadherin expression in pancreatic cancer: Correlation with lymph node metastasis,high grade,and advanced stage

Epithelial cadherin (E-cadherin) is a Ca²⁺-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumours. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumours (grade I) (4/14, 28 per cent) (P=0·012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P=0·043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer.     

宫颈上皮内瘤变及宫颈鳞癌中cyclin D1、Ki-67的表达及其意义

目的： 检测细胞周期素D1（cyclin D1）、增殖细胞核抗原（Ki-67）在人乳头瘤病毒（HPV）感染患者宫颈上皮内瘤样病变（CIN）及宫颈鳞癌中的表达及其相关性,研究其在CIN及宫颈鳞癌发生及发展过程中的作用。方法: 研究组HPV阳性病理确诊CINⅠ17例、CINⅡ19例、CINⅢ23例、宫颈鳞癌23例,对照组HPV阳性病理确诊柱状上皮异位22例。应用免疫组化S-P法检测宫颈病变组织中cyclin D1、Ki-67蛋白的表达,杂交捕获二代检测宫颈分泌物中HPV感染的情况。结果: (1)Cyclin D1在5组宫颈组织细胞的细胞核内均有表达,CINⅢ组、宫颈鳞癌组与对照组比较差异显著（P<0.05）,CINⅢ组、宫颈鳞癌组与CINⅠ组比较差异显著（P<0.05）,宫颈鳞癌组与CINⅡ组比较差异显著（P<0.05）。(2)Ki-67在5组宫颈组织细胞的细胞核内均有表达,对照组与CINⅢ组比较差异显著（P<0.05）,对照组与宫颈鳞癌组比较差异显著（P<0.05）,CINⅠ组与宫颈鳞癌组比较差异显著（P<0.05）,CINⅡ组与宫颈鳞癌组比较差异显著（P<0.05）。(3)Cyclin D1、Ki-67在CIN及宫颈鳞癌中的表达强度呈正相关关系 （P<0.05）。结论: Cyclin D1和Ki-67在CIN和宫颈鳞癌发生发展及细胞增殖活动中起一定的作用;两者在CIN和宫颈鳞癌的发生发展中可能发挥协同作用。     

E-cadherin expression in follicular carcinoma of the thyroid

Follicular carcinoma (FC) of the thyroid is distinguished from follicular adenoma (FA) by confirmation of invasion or metastasis. However, it is still unknown how FC acquires the potential for invasion or metastasis. Twenty early FC (pT1 and pT2) were analyzed for immunohistochemical E-cadherin (E-CD) expression. Four of four (100%) widely invasive FC showed reduced E-CD expression, whereas only two of 16 minimally invasive FC showed reduced expression. In most of the minimally invasive FC, both E-CD and beta-catenin were expressed on cell-cell boundaries, even in areas where capsular invasion occurred. These results suggest that the mechanism of invasion may be different between widely invasive FC and minimally invasive FC, and that E-CD is probably responsible for the invasion of widely invasive FC. Analysis of methylation of the E-CD gene promoter using the methylation-specific polymerase chain reaction (MSP) method revealed no methylated alleles in the DNA from FC.     

Platelet-derived endothelial cell growth factor expression and angiogenesis in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix

Growth and metastatic spread of invasive carcinoma depends on angiogenesis, the formation of new blood vessels. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic growth factor for a number of solid tumors, including lung, bladder, colorectal, and renal cell cancer. Cervical intraepithelial neoplasia (CIN) is the precursor to squamous cell cervical carcinoma (SCC). Mean vessel density (MVD) increases from normal cervical tissue, through low- and high-grade CIN to SCC. We evaluated PD-ECGF immunoreactivity and correlated its expression with MVD in normal, premalignant, and malignant cervical tissue. PD-ECGF expression was assessed visually within the epithelial tissues and scored on the extent and intensity of staining. MVD was calculated by counting the number of vessels positive for von Willebrand factor per unit area subtending normal or CIN epithelium or within tumor hotspots for SCC. Cytoplasmic and/or nuclear PD-ECGF immunoreactivity was seen in normal epithelium. PD-ECGF expression significantly increased with histologic grade from normal, through low- and high-grade CIN, to SCC (P < .02). A progressive significant increase in the microvessel density was also seen, ranging from a mean of 28 vessels for normal tissue to 57 for SCC (P < .0005). No correlation was found between PD-ECGF expression and MVD (P = .45). We conclude that PD-ECGF expression and MVD increase as the cervix transforms from a normal to a malignant phenotype. PD-ECGF is thymidine phosphorylase, a key enzyme in the activation of fluoropyrimidines, including 5-fluorouracil. Evaluation of PD-ECGF thymidine phosphorylase expression may be important in designing future chemotherapeutic trials in cervical cancer.     

hCTR1、FHIT与PCNA在子宫颈上皮内瘤变和子宫颈鳞癌中表达及意义

目的观察人类铜转运蛋白(human copper transporters 1,hCTR1)、脆性组氨酸三联体(fragile histidine triad,FHIT)和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及子宫颈鳞癌(squamous cell carcinoma,SCC)中的表达,探讨SCC中三指标之间的相关性。方法采用免疫组化SP法检测94例CIN、40例SCC及23例正常宫颈组织中hCTR1、FHIT和PCNA的表达。结果 (1)hCTR1在SCC(87.50%)及CIN 2～3(74.63%)的阳性率均明显高于正常组(17.39%)、CIN 1(29.63%),差异有统计学意义(P<0.001)。(2)FHIT从正常组(100%)、CIN 1(74.07%)、CIN 2～3(44.78%)到SCC(32.50%),FHIT阳性细胞表达逐渐减少。FHIT在各组间阳性率比较差异有统计学意义(P<0.001);FHIT阳性率在SCC及CIN组明显低于正常组中的表达,差异有统计学意义(P<0.001);FHIT阳性率在CIN 2～3与CIN 1之间的表达,差异有统计学意义(P<0.05)。(3)PCNA在CIN 2～3(64.18%)、SCC(75.00%)中阳性表达,明显高于正常组(26.09%),差异有统计学意义(P<0.05,P<0.001);CIN 2～3与CIN 1之间PCNA阳性率差异有统计学意义(P<0.05)。(4)在SCC中FHIT和PCNA表达具有负相关性(P<0.05,r=-0.377);hCTR1与PCNA、FHIT的表达之间均无相关性(P>0.05),r hCTR1与PCNA=0.026,r hCTR1与FHIT=-0.296。结论 (1)hCTR1在子宫颈原位癌阳性细胞比率要高于子宫颈早期浸润癌中hCTR1的表达。提示hCTR1与恶性肿瘤生物学特征侵袭可能存在负相关性。(2)FHIT蛋白和PC-NA共同参与调节细胞增殖,二者存在一种平衡关系。检查子宫颈CIN中的FHIT和PCNA蛋白表达情况,可用作高级别的CIN筛查或预测。     

E-cadherin在结直肠癌中的表达及其与侵袭转移的关系

目的：探讨E-cadherin在结直肠癌（colorectal carcinoma,CRC）中的表达及其与侵袭转移的关系。方法：采用免疫组织化学SABC法及原位杂交技术检测E-cadherin mRNA和蛋白在大肠正常黏膜、大肠腺瘤和CRC组织中的表达。结果： E-cadherin的mRNA和蛋白在CRC中的阳性率显著低于正常黏膜组织和腺瘤（P＜0.01）;随着CRC分化的降低和Dukes分期的增加,E-cadherin表达阳性率降低;E-cadherin的阳性率在有淋巴结和远处器官转移的CRC中均显著低于未转移组（P＜0.01,P＜0.05）。结论：E-cadherin表达减少或缺失在CRC的侵袭转移过程中发挥重要的作用。     

喉鳞状细胞癌中FAK和E-cadherin的表达及意义

目的 探讨粘着斑激酶(FAK)和E-钙黏蛋白(E-cadherin)在喉鳞状细胞癌(LSCC)组织中的表达与肿瘤的病理学分级及颈淋巴结转移之间的关系.方法 应用逆转录多聚酶链反应(RT-PCR)和免疫组化sP法检测LSCC和癌旁组织中FAK和E-cadherin表达情况.结果 在癌和癌旁组织中,FAK和E-cadherin mRNA的相对表达量差异具有显著性(P<0.05),且两者的表达与LSCC的淋巴结转移相关(P<0.05).E-cadherin mRNA相对表达量与肿瘤病理学分级相关(P<0.01).在癌及癌旁组织中FAK和E-cadherin的蛋白表达差异具有显著性(P<0.01),并且与颈部淋巴结转移有关(P<0.05);E-cadherin蛋白表达与肿瘤病理学分级相关(P<0.05).FAK与E-cadherin在mRNA水平或蛋白水平其表达呈负相关(r=-0.287,P<0.05;r=-0.287,P<0.05).结论 FAK的表达增高与E-cadherin的表达降低可能参与了LSCC的发生过程,是LSCC恶性程度及侵袭转移的重要标志物,对预测LSCC预后具有重要意义.     

Expression of E-cadherin and vimentin in oral squamous cell carcinoma

The aim of the study is to determine the levels of E-cadherin, vimentin expression in tumor tissues from patients with oral squamous cell carcinoma (OSCC), and the relationship between the expression of E-cadherin, vimentin and epithelial-mesenchymal transition, in order to explore its values for predicting the invasion and metastasis of oral squamous cell carcinoma, short survival of patients in many types of cancer. E-cadherin and vimentin expression of 10 benign and 42 OSCC tumor tissues was examined by immunohistochemical staining. E-cadherin is positively expressed in normal oral mucosa epithelium, but vimentin expression is not found in normal oral mucosa epithelia; the E-cadherin and vimentin were expressed in 26 of 42 (61.9%) and 16 of 42 (38.1%), respectively. No statistically difference was found for E-cadherin and vimentin expression in patients with different age, gender and tumor location, E-cadherin and vimentin expression was significantly associated with lymph node metastasis and tissue location (P < 0.05); E-cadherin expression was also significantly associated with tumor stage (P < 0.05); there are significantly difference between infiltrative margin and central area in patients with oral squamous cell carcinoma for E-cadherin and vimentin positive expression (P < 0.05). E-cadherin and vimentin positive expression was associated with tumor metastasis of oral squamous cell carcinoma. Our study preliminarily confirmed that EMT phenomenon is existed during the development of oral squamous cell carcinoma. Co-evaluation of E-cadherin and vimentin might be a valuable tool for predicting OSCC patient outcome.     

Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma

Vulvar squamous cell carcinoma (VSCC) accounts for >90% of the malignant tumours of the vulva. Most VSCCs originate in intraepithelial lesions, named vulvar intraepithelial neoplasia (VIN), that precede the development of VSCC by a variable period of time. Strong evidence has accumulated showing that there are two different aetiopathogenic pathways for the development of VSCC and VIN, one associated with infection by human papillomavirus (HPV), and a second independent of HPV infection. These two different types of VSCC have different epidemiological, pathological and clinical characteristics, and should therefore be considered as two separate entities. Histologically, HPV‐associated VSCCs are of the basaloid or warty type, and arise from VIN of the usual type. Inactivation of p53 and the retinoblastoma tumour suppressor gene product by the viral gene products E6 and E7 is involved in the process of malignant transformation. HPV‐independent VSCCs are histologically keratinizing, are associated with differentiated VIN and lichen sclerosus, and frequently show mutations of p53. p16^INK4a and p53 immunostaining can be useful for classifying VSCC into HPV‐associated or HPV‐independent. Although large, multicentre studies are needed to definitively assess the involvement of HPV in the prognosis of VSCC, most studies have not found clear differences in survival between HPV‐associated and HPV‐independent tumours.     

CD34(+) fibrocytes in normal cervical stroma,cervical intraepithelial neoplasia III,and invasive squamous cell carcinoma of the cervix uteri

CD34(+) fibrocytes are widely distributed in normal connective tissues but have been reported to be absent within the stroma associated with invasive carcinomas. In the present study we investigated the presence and distribution of CD34(+) fibrocytes and alpha-smooth muscle actin (alpha-SMA) positive myofibroblasts in cervical intraepithelial neoplasia III (CIN III; n=8), invasive carcinoma of the cervix ( n=18) and adjacent normal cervical stroma. Normal cervical stroma and the stroma adjacent to CIN III disclosed a dense network of CD34(+) fibrocytes, whereas the stroma of invasive carcinoma was virtually free of this cell population. Early stromal invasion by squamous carcinoma was characterized by a focal loss of CD34(+) fibrocytes. alpha-SMA-positive myofibroblasts were not seen in the normal cervical stroma but occurred in six of eight cases of CIN III adjacent to the atypical epithelium. The stroma of invasive carcinoma was made up of large amounts of haphazardly arranged alpha-SMA-positive myofibroblasts. In the setting of the present study, a loss of CD34(+) fibrocytes was specific for stromal alterations associated with invasive carcinoma and proved to be a sensitive tool in detecting small foci of stromal invasion. Therefore, detection of a loss of CD34(+) fibrocytes may constitute an adjunctive tool in detecting (1) early stromal invasion and (2) invasive carcinoma in small biopsy specimens. Moreover, the present study shows that CD34(+) fibrocytes and myofibroblasts play an important role in stromal remodeling associated with invasive squamous cell carcinoma of the cervix.     

E-cadherin expression in invasive non-lobular carcinoma of the breast and its prognostic significance

BACKGROUND: E-cadherin is a cell adhesion molecule that is expressed in normal breast tissue and is often considered useful as a phenotypic marker in breast cancer diagnosis, with absence of its expression frequently observed in tumours of lobular subtype. However, the clinicopathological and prognostic value of E-cadherin in the more frequent non-lobular types of breast carcinoma is unclear. METHODS AND RESULTS: E-cadherin expression was assessed immunohistochemically in a large and well-characterized series of invasive non-lobular breast carcinoma types (n=1665) with long-term clinical follow-up (median 56 months) using tissue microarray technology, to determine the relationship between its expression and primary tumour characteristics and disease outcome. Only membranous expression of E-cadherin was considered in this study and its expression was categorized as normal (H-score>100) or reduced [absent or below the median (score相似文献   

Significance of dysadherin and E-cadherin expression in differentiated-type gastric carcinoma with submucosal invasion

Dysadherin is a cancer-associated cell membrane glycoprotein that down-regulates E-cadherin and plays important roles in tumor progression and metastasis. Differentiated-type gastric carcinoma can be classified into 2 histologic subtypes according to the presence of poorly differentiated components: a mixed type (differentiated carcinoma with poorly differentiated components) and a pure type (purely differentiated-type adenocarcinoma). We studied the clinicopathologic features of 318 cases of differentiated-type gastric carcinoma with submucosal invasion and evaluated the immunohistochemical expression of dysadherin and E-cadherin. We also evaluated 46 cases of metastatic lymph nodes. Tumors with combined dysadherin-positive (≥50%) expression and E-cadherin-negative (<50%) expression had significantly higher proportions of the moderately differentiated type, deeper submucosal invasion, positivity of lymphatic permeation, and positivity of lymph node metastasis than tumors with other combinations of dysadherin and E-cadherin expression (P = .0009, P = .0015, P = .0273, and P = .0187, respectively). Moreover, the frequency of dysadherin-positive (≥50%) expression was higher in the mixed type (60.3%) than in the pure type (12.4%) (P < .0001), whereas the frequency of E-cadherin-negative (<50%) expression was higher in the mixed type (84.5%) than in the pure type (50.5%) (P < .0001). The frequency of dysadherin expression in the metastatic lymph nodes (80.4%) was significantly higher than that in the primary tumors (45.7%) (P = .001). Dysadherin-positive (≥50%) expression and E-cadherin-negative (<50%) expression may be correlated with the mixed type. Combined dysadherin-positive (≥50%) expression and E-cadherin-negative (<50%) expression may be valuable information for predicting aggressive tumor behavior.     

E-cadherin的表达与肝细胞癌侵袭和转移的关系

目的研究上皮性钙黏蛋白（E-cadherin）在人肝细胞癌（HCC）中的表达情况,探讨其与肝癌的相关性。方法选择56例有完整随访资料的肝细胞癌及相应癌旁组织标本、20例正常肝组织标本,用RT-PCR方法检测E-cadherinmRNA的表达;用免疫组织化学方法检测E-cadherin的表达。结果①E-cadherin在肝细胞癌组织中的表达显著低于癌旁组织和正常组织（P〈0．05）,而在癌旁组织和正常组织中的表达无差异;②E-cadherin在肝癌组织中的表达与术后复发时间呈正相关（P〈0．05）,与病理分期呈负相关（P〈0．05）;③癌组织中E-cadherin表达与肝外转移呈负相关（P〈0．05）;④癌旁组织中E-cadherin表达与术后复发时间呈正相关（P〈0．05）。结论E-cadherin表达缺失或下调与肝癌的分化程度、侵袭转移能力和复发倾向相关,对肝癌临床转归的评估有一定指导意义。