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1.
Alteration in expression of E-cadherin and catenins is associated with loss of differentiation, acquisition of an invasive phenotype and poor clinical outcome in many types of cancer. To identify molecular prognostic markers, membrane expression levels of E-cadherin, and alpha-, beta- and gamma-catenin in biopsy samples (n=135) of oral squamous cell carcinoma (OSCC) were evaluated immunohistochemically in relation to preoperative tumour-related features, clinical course and prognostic value, and were found to be significantly correlated with an endophytic growth pattern and pathologically proved lymph-node metastasis. Alteration of expression of E-cadherin, and alpha-, beta- and gamma-catenin was also significantly correlated with poor disease-specific 5-year survival (P=0.0096, 0.0434, 0.0005 and 0.0005, respectively). Multivariate Cox proportional hazard regression analysis showed that alteration of beta- and gamma-catenin expression was a significantly independent prognostic parameter for survival (P=0.0112 and 0.0088, respectively), as was the case with endophytic growth pattern and advanced N-category. These results indicate that patients with OSCC and absent or reduced membrane expression of beta- and gamma-catenin should be considered a high-risk group for regional lymph-node metastasis and poor prognosis.  相似文献   

2.
BACKGROUND: The main cause of treatment failure in resectable oral squamous cell carcinoma (OSCC) is metastasis. E-cadherin (E-cad) plays a principal role in cell adhesion and motility, and is associated with OSCC progression. The aim of this study was to investigate the clinical significance of E-cad expression in OSCC with lymph node metastasis which had radical neck dissection done. METHOD: Immunohistochemistry was used to detect E-cad expression in normal oral mucosa (NOM) (n = 10), oral precancerous lesions (OPLs) (n = 20), primary OSCC (n = 45), and their paired metastatic lesions (n = 45). E-cad immunoreactivity correlated with the clinicopathologic features. RESULTS: E-cadherin immunoreactivity was progressively reduced in the NOM followed by OPLs and primary OSCC (58%). It decreased significantly in the advanced stages of OSCC. However, the increase in E-cad immunoreactivity was observed in the majority (60%) of metastatic lesions in relation to primary OSCC. Patients with such increased or positive immunoreactivity of E-cad in metastatic lesions exhibited worse prognosis. CONCLUSION: The findings suggested a dynamic change in E-cad immunoreactivity during tumorigenesis and metastasis of OSCC. In a multivariate analysis, E-cad immunoreactivity in metastasis lesions (odds ratio 3.74, 95% CI 1.15-14.67; P = 0.040) implied the potential role of mortality predictors for OSCC cases with nodal involvement.  相似文献   

3.
目的 研究舌鳞状细胞癌(舌癌)中上皮钙黏蛋白(E-cadherin,E-cad)、β-连环素(β-catenin)的表达,探讨其在舌癌复发及预后中的意义.方法 采用免疫组化半定量方法检测30例舌癌患者肿瘤组织中E-cad与β-连环素的表达,同时通过随访资料分析其表达水平与临床病理及预后之间的关系.结果 63%(19/30)的癌组织中E-cad呈低表达;60%(18/30)癌组织中β-连环素高表达.E-cad、β-连环素表达水平与患者的性别、年龄、肿瘤分化程度、大小、临床分期、淋巴结转移比较,差异无统计学意义;E-cad表达与肿瘤复发比较,差异有统计学意义(P=0.007),而β-连环素表达与肿瘤复发比较,差异无统计学意义(P>0.05).单因素Cox回归预后分析显示E-cad的表达与生存率比较,差异有统计学意义(P=0.018).结论 E-cad表达降低与肿瘤复发及术后生存率之间密切相关,可作为舌癌患者预后的预测指标.  相似文献   

4.
Oral squamous cell carcinoma (OSCC) is one of the most common malignances. In epithelial-mesenchymal transition (EMT), epithelial cells switch to mesenchymal-like cells exhibiting high mobility. This migratory phenotype is significant during tumor invasion and metastasis.

Objective

: The aim of this study is to evaluate the expression of the EMT markers E-cadherin, N-cadherin and vimentin in OSCC.

Material and Methods

: Immunohistochemical detection of E-cadherin, N-cadherin and vimentin was performed on 20 OSCC samples. Differences in the expression of each protein at the invasive front (IF) and in the central/superficial areas (CSA) of the tumor were assessed. Differences in the expression of each protein at the IF of both histologically high- and low-invasive OSCCs were evaluated. Associations among expression of proteins at the IF were assessed. Correlations between the expression levels of each protein at the IF and the tumor stage and clinical nodal status were also evaluated.

Results

: Reduced expression of E-cadherin was detected in 15 samples (75%). E-cadherin expression was reduced at the IF when compared to the CSA and in high-invasive tumors when compared to low-invasive tumors. All samples were negative for N-cadherin, even though one sample showed an inconspicuous expression. Positive expression of vimentin was observed in 6 samples (30%). Nevertheless, there was no difference in vimentin expression between the IF and the CSA regions or between the low- and high-invasive tumors. Furthermore, no association was observed among protein expression levels at the IF. Finally, no correlations were observed between each protein’s expression levels and tumor stage or clinical nodal status.

Conclusions

: Reduced E-cadherin expression at the IF and its association with histological invasiveness suggest that this protein is a noteworthy EMT marker in OSCC. Although vimentin was also detected as an EMT marker, its expression was neither limited to the IF nor was it related to histological invasiveness.  相似文献   

5.
OBJECTIVES: To evaluate the expression of E-cadherin, a calcium-dependent cell adhesion molecule, in a retrospective analysis of paraffin embedded tissue specimens of oral squamous cell carcinoma and relationship with the clinical TNM stage and histochemical differentiation. DESIGN: Paraffin embedded tissue sections of normal oral mucosa ( n = 6), oral squamous cell carcinoma (SCC, n = 18) and metastatic lymph nodes ( n = 2) were immunostained by a three-stage streptoavidin-biotin immunoperoxidase method using monoclonal antibody. The TNM staging and histochemical grading were done according to the standard criteria.
RESULTS: Normal oral epithelium showed a strongly positive pericellular distribution of E-cadherin in basal, parabasal and spinous layers and no staining was observed in the parakeratinized and cornified layerS. In well differentiated SCCs, the centrally located cells in tumour islands showed no staining, but peripheral basally located tumour cells showed positive staining. Poorly differentiated SCCs were devoid of staining. In moderately differentiated SCCs, the staining pattern was found to be one of the following three types: (1) a pattern similar to that of well differentiated SCC; (2) central cells of tumour aggregates were reactive but peripheral cells showed weak to negative reaction; and (3) all cells showed a negative reaction, resembling the poorly differentiated SCC.Fischer exact test showed a statistically significant correlation with loss of E-cadherin and grades of tumour differentiation as well as an advancing T and N stage.
CONCLUSION: The loss of E-cadherin may correlate with advancing T and N stages of the tumour and a poor tumour cell differentiation in oral squamous cell carcinomas.  相似文献   

6.
Protease-activated receptor 1 (PAR1) is known as a thrombin receptor. Recent studies have reported PAR1 expression in various malignancies; however, its role in oral squamous cell carcinoma (OSCC) requires clarification. A previous study showed that down-regulation of ΔNp63, a homolog of p53, augments PAR1 expression in OSCC. In the present study, the association of PAR1 expression with clinicopathological findings in OSCC was examined retrospectively. Expression of PAR1, thrombin, and ΔNp63 was examined immunohistochemically in OSCC specimens. Patients were divided into three groups based on the expression pattern of PAR1 at the invasive front: group A, PAR1-negative in both cancer and stromal cells; group B, positive in stromal cells but negative in cancer cells; group C, positive in both cancer and stromal cells. Histologically high-grade tumours were significantly more common in group C. Patients in group C had the highest incidence rate of nodal metastasis (P < 0.001) and a lower survival rate (P = 0.085) than those in the other groups. At the invasive front, in group C, thrombin was expressed but ΔNp63 expression was weak. These results indicate that increased PAR1 expression in both cancer and stromal cells could be a useful predictive marker of nodal metastasis and that ΔNp63 is involved in regulating PAR1 expression.  相似文献   

7.
Regulatory T cells (Tregs) and tumour-associated macrophages (TAMs) contribute to the tumour microenvironment by inhibiting anti-tumour immune responses. This study was performed to investigate the roles of Tregs and TAMs in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPL). The expression of Treg markers CD25 and FoxP3 and TAM markers CD163 and CD204 was investigated in 82 OSCC and 45 OEPL specimens, and their associations with clinicopathological parameters were analyzed. Correlations were found among CD25, FoxP3, CD163, and CD204 levels (P < 0.001), and these targets were up-regulated in OSCC compared to OEPL (P < 0.001). In OSCC, infiltration of Tregs and/or M2 TAMs was associated with sex and clinicopathological features, such as tumour size, nodal metastasis, tissue differentiation, stromal reaction, invasive behaviour, and invasive depth. In OEPL, CD25, FoxP3, CD163, and CD204 immunoreactivities were significantly associated with sex, postoperative recurrence, and cancerization to OSCC. This study is novel in showing that the infiltration of Tregs and M2 TAMs is significantly associated with the progression of premalignant lesions to OSCC. This suggests that these cells represent prognostic biomarkers for premalignant lesion progression and that immunotherapeutic approaches to control Treg/M2 TAM numbers could protect against progression to malignancy.  相似文献   

8.
目的检测微卫星位点TP53、RPS6在口腔鳞癌浸润前沿、中心及癌间质细胞中的基因变化,揭示口腔鳞癌的生物学行为。方法运用激光捕获显微切割分别获取同一肿瘤浸润前沿、中心及癌间质足量的细胞,提取DNA,PCR-变性PAGE电泳检测TP53和RPS6位点的基因变化。结果浸润前沿、中心和癌间质中TP53和RPS6存在杂合性缺失(10ssofheterozygosity,LOH)和微卫星不稳定(microsatelliteinstability,MI),发生率从23.5%(4/17)到64.7%(11/17),且LOH和(或)MI的模式存在不同。上皮TP53和RPS6的LOH和MI发生率分别为70.6%(12/17)和64.7%(11/17),间质为43.8%(7/16)和23.5%(4/17),癌实质较间质发生率高,差异有统计学意义(P〈0.05)。浸润前沿TP53的LOH发生率为64.7%(11/17),中心为60.0%(9/15)。RPS6在浸润前沿的LOH和MI为58.8%(10/17),中心为29.4%(5/17)。两位点总发生率分别为62.5%(20/32)和44.1%(15/34),差异有统计学意义(P〈0.05)。结论部分口腔鳞癌样本浸润前沿、中心和肿瘤间质的基因变化不同,癌实质基因变化率与肿瘤分化程度有关。  相似文献   

9.
口腔鳞癌粘着斑激酶表达与颈淋巴结转移关系的研究   总被引:1,自引:3,他引:1  
目的 :探讨粘着斑激酶 (FAK)在口腔粘膜鳞状细胞癌中的表达特点及其与颈淋巴结转移的关系。方法 :应用免疫组化LsAB法检测FAK在口腔癌原发灶及颈淋巴结转移灶中的表达分布特点 ,并与颈淋巴结转移的发生进行相关性分析。结果 :80例口腔癌原发灶均有FAK表达 ,口腔癌生长前沿区细胞的表达明显强于中央区 (P <0 .0 1) ,呈条带状分布 ;FAK在转移灶中的表达强度与原发灶前沿区细胞一致 ;口腔癌前沿区细胞FAK表达强度与颈淋巴结转移的发生呈正相关 (P <0 .0 5 ) ,而中央区FAK表达强度与颈淋巴结转移无关 (P >0 .0 5 )。结论 :FAK在口腔癌中的表达主要分布于生长前沿区细胞 ,参与癌细胞的侵袭性行为 ,与口腔癌颈淋巴结转移的发生有关  相似文献   

10.
BACKGROUND: Glutamate activates the N-methyl-d-aspartate (NMDA) receptors and this receptor is involved in the proliferation and migration of various tumour cells in vitro. However, the relationship between NMDA receptor expression and clinical parameters in cancer patients is unclear. Therefore, NMDA receptor 1 (NMDAR1) expression along with its clinical significance was examined in patients with oral squamous cell carcinoma (OSCC). METHODS: Eighty-one tumour specimens from OSCC patients were used to determine the NMDAR1 expression level by immunohistochemical staining. The control was obtained from a matched normal adjacent mucosa. The cases were considered to be positive if reactivity was displayed in >25% of the cells. RESULTS: The NMDAR1 reactivity was positive in 50 of 81 cases, while it was negative in the control. NMDAR1 expression was significantly associated with a lymph node metastasis (P = 0.008), the tumour size (P < 0.001), and the cancer stage (P = 0.034). The patients whose tumours expressed NMDAR1 had a significantly poorer survival than the patients who were NMDAR1-negative (log-rank = 6.45, d.f. = 1, P = 0.011). CONCLUSIONS: The NMDAR1 overexpression was significantly associated with the prognosis-related factors. Therefore, it might be one of the prognostic markers of OSCC.  相似文献   

11.
BACKGROUND: Recent years have witnessed an increasing emphasis on the role of nuclear DNA and its application in experimental pathological diagnosis to predict prognosis and management of certain neoplasm. AIMS: to establish objective criteria for the degree of differentiation and histochemical quantitative of nuclear DNA of oral squamous cell carcinoma (OSCC) using microspectrophotometric analysis. MATERIAL AND METHODS: The study was conducted on histologic materials from patient with OSCC. Two histological grading systems were used; Broder's and invasive front grading system were recorded. Microspectrophotometry was applied on Feulgen-stained sections to determine the quality of tumour nuclear DNA content in two different histological grading systems of OSCC. RESULTS: Nuclear DNA content increased significantly with decreasing tissue differentiation as well with increasing tumour size. CONCLUSION: The grading system and DNA content provides more objective and accurate criteria which relate the morphologic finding to biologic activity and growth patterns of oral cancer as compared to histologic differentiation alone.  相似文献   

12.
BACKGROUND: Alteration of cadherin and catenin expression is associated with loss of differentiation, acquisition of an invasive phenotype, and poor prognosis in many types of cancers. The roles of cadherins and catenins in mucoepidermoid carcinoma (MEC) are not fully understood. METHODS: Based on immunohistochemical studies, the expressions of E-, N-, and P-cadherins and alpha-, beta-, and gamma-catenins in MEC were investigated, and correlations with clinicopathologic parameters were evaluated. RESULTS: These six molecules were strongly expressed in normal ductal epithelium but increased or decreased immunoreactivities of those proteins in MEC were frequently observed, especially for E-cadherin and alpha-catenin. The immunoactivity of beta-catenin showed significant correlation with grade (P = 0.05) and stage (P < 0.0001). beta-Catenin expressions are also correlated with gamma-catenin expression (P = 0.006) according to cross-table analysis. Survival analysis indicated that stage, grade, and beta-catenin expressions had significant correlation with survival. CONCLUSION: Aberrant beta-catenin expression may play an important role in the histologic differentiation and tumor staging of MEC.  相似文献   

13.
BACKGROUND: It is hypothesised that cell proliferation, as measured by the Ki-67 labelling index (LI) at the invasive tumour front (ITF) was directly related to the histological grade in human oral squamous cell carcinomas (SCCs). METHODS: Tissues from 42 human oral SCCs were collected and stained with an antibody directed against the Ki-67 antigen using an advanced polymer staining system. Quantitation of the immunopositive cells was performed on two parallel sections at the invasive tumour front (ITF), using an image analyser. The Ki-67 LI was expressed as the number of positive nuclei/mm2 of epithelium. The control tissue used was normal epithelium at the excision margin. RESULTS: The mean Ki-67 LI for oral SCCs at the ITF was significantly greater than that for the excision margin tissue (P < 0.0001). There was a positive association between increasing Ki-67 LI and increasing Broders' grade (P < 0.05), with a well-differentiated tumour having the lowest mean Ki-67 LI (1549 +/- 806) and a poorly differentiated tumour having the highest value (2232 +/- 771). A similar trend was observed between the mean Ki-67 LI and Bryne's multifactorial grading system. CONCLUSIONS: It was concluded from this study that cell proliferation (as measured by the Ki-67 antigen) at the ITF had a strong positive relationship with histological grading in human oral SCC.  相似文献   

14.
Background: The aim of this study was to describe the human mutS homolog 2 (hMSH2) and human mutL homolog 1 (hMLH1) immunoexpression in different areas of oral squamous cell carcinoma (OSCC) – central/superficial (C/S) and invasive tumor front (ITF) – in an attempt to verify if the histological grade of malignancy interferes in this expression. Methods: Forty‐six samples of OSCC were analyzed histologically. Twenty‐six cases (56.5%) presented ITF. Histological grades of malignancy were evaluated in all samples, and immunohistochemistry was applied using specific antibodies against hMSH2 and hMLH1 proteins. Immunoexpression was semiquantitatively scored, and results were correlated with their histological grades of malignancy. Results: The hMSH2 immunoexpression in both C/S and ITF was not correlated with histological grades of malignancy, whereas hMLH1 overexpression was correlated (P = 0.043) and associated (P = 0.041) with well‐differentiated tumors. In addition, hMHL1 reduction or negative expression was detected in poorly differentiated tumors. Moreover, negative expression for hMSH2 and hMLH1 proteins was demonstrated in some cases of OSCC. Conclusions: The findings of the present study indicate that the histological grade of malignancy interferes in hMLH1 immunoexpression. The negativity for both hMSH2 and hMLH1 proteins in some cases suggests a possible association between OSCC and hereditary non‐polyposis colorectal cancer. Further investigation from future studies is needed to elucidate this supposition.  相似文献   

15.
BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in oral and maxillofacial region with poor prognosis. E-cadherin plays a key role in cell-to-cell adhesion. E-cadherin expression in the metastatic cervical lymph node, especially in the micrometastatic cervical lymph node has seldom been reported in OSCC patients. OBJECTIVE: To investigate the E-cadherin expression in cervical lymph nodes from OSCC patients as well as its clinical significance. DESIGN: Thirty-three OSCC patients were involved in this study; among them, there were 28 males and 5 females, the age ranged from 34 to 78 years (mean 58.8 years). The most suspicious metastatic cervical lymph node (total 99 lymph nodes) from three cervical regions of each OSCC patient was selected for detection of E-cadherin using routine pathological examination and immunohistochemistry. RESULTS: Increased E-cadherin expression in the metastatic cervical lymph nodes was detected, which was diagnosed by routine pathological examination using HE staining. However, in the micrometastatic cervical lymph node, E-cadherin expression was negative. The survival rate of OSCC patients correlated with decreased E-cadherin expression (P=0.001), N stage (P=0.024) and tumor recurrence (P<0.001). Tumor recurrence is the only independent factor on the prognosis (RR=20.83 and P=0.014). CONCLUSIONS: Decreased E-cadherin expression in cancerous tissue correlates with the poor prognosis of OSCC patients. Detection of E-cadherin expression is useful to confirm the cervical lymph node metastasis and maybe useless to detect the cervical lymph node micrometastasis; further studies are encouraged to reveal the detail mechanism of E-cadherin expression in formation of lymph node metastatic focus.  相似文献   

16.
17.
目的 观察人口腔鳞状细胞癌(OSCC)组织中上皮间质化相关蛋白及转录因子Twist的表达,研究Twist在OSCC上皮间质化中的作用及OSCC转移情况的相关性,并探讨其在人OSCC中的临床意义。方法 通过免疫组织化学及原位杂交的方法分别检测30例OSCC组织中上皮源性标记物E-钙黏蛋白(E-cad)和细胞角蛋白(CK),间质源性标记物N-钙黏蛋白(N-cad),转录因子Twist蛋白及mRNA的表达情况,并与临床病理资料作对照分析。结果 免疫组织化学结果:在OSCC组织中,Twist、N-cad的表达明显高于正常组织,E-cad及CK的表达明显低于正常组织(P<0.05);在OSCC中低分化组,Twist、N-cad的表达高于高分化组,E-cad及CK的表达明显低于高分化组(P<0.05);在有淋巴结转移组中,Twist、N-cad的表达高于无淋巴结转移组,E-cad及CK的表达低于无淋巴结转移组(P<0.05)。原位杂交结果:Twist mRNA在OSCC中低分化组,T3、T4组和有转移淋巴结组的表达分别高于高分化组,T1、T2组和无淋巴结转移组,以上差异均有统计学意义(P<0.05)。结论 OSCC组织中存在上皮间质化,Twist可使肿瘤细胞的侵袭力增加,促进OSCC的浸润和转移。联合检测Twist、E-cad和N-cad的表达可能会更有效地判断和预测OSCC的转移。  相似文献   

18.
目的:探讨E-钙黏蛋白(E-cadherin)和波形蛋白(Vimentin)在口腔鳞状细胞癌(OSCC)上皮-间质转化中的作用及表达。方法:选取76例口腔鳞状细胞癌(OSCC)患者和40例健康者作为对照组,利用RT-PCR检测OSCC和正常口腔黏膜组织中TGF-β1、E-cadherin和Vimentin表达。结果:OSCC患者组织中TGF-β1 mRNA和Vimentin mRNA相对表达量均高于对照组,而E-cadherin mRNA相对表达量低于对照组,差异均有统计学意义(P<0.05);TGF-β1、E-cadherin和Vimentin在OSCC组织中表达均与分化程度有关,分化程度越高,TGF-β1 mRNA和Vimentin mRNA相对表达量越高,而E-cadherin mRNA相对表达量则越低;Pearson相关分析显示,OSCC中TGF-β1 mRNA相对表达量与E-cadherin mRNA相对表达量呈负相关(r=-0.322,P=0.004),而与Vimentin mRNA相对表达量呈正相关(r=0.661,P=0.000)。结论:TGF-β1和Vimentin 在OSCC组织中表达增强,而E-cadherin则表达降低,提示EMT过程在OSCC发生及进展过程中发挥重要作用。  相似文献   

19.
The aim of this study was to evaluate the rare postoperative supraclavicular metastasis originating from oral squamous cell carcinoma (OSCC) and to discuss epidermal growth factor receptor (EGFR) as a potential predictive marker. Tumour specimens of OSCC patients divided into three groups were included: supraclavicular metastasis (n = 8), conventional cervical metastasis (n = 28), no metastasis (n = 48). Basic information and EGFR expression were compared among these groups and the data were analysed to identify potentially related risk factors for supraclavicular metastasis. In the supraclavicular metastasis group (n = 8), all primary tumours were T1–T2 and located in the tongue and buccal region; five of eight cases were pathologically N0. The median interval from the primary tumour resection to the development of supraclavicular metastases was 21.5 months. All related deaths (5/8) occurred within 2 years. In the supraclavicular metastasis group, EGFR expression was highest in the supraclavicular metastases, followed by cervical lymph nodes, and was lowest in the primary tumours (P = 0.39). In contrast, in the conventional metastasis group and the N0 group, EGFR expression was higher in the primary tumours than in the lymph nodes (P < 0.01). Supraclavicular metastasis of OSCC is infrequent and associated with a poor prognosis. EGFR might predict the occurrence of supraclavicular metastasis.  相似文献   

20.
目的:观察Periostin在口腔鳞状细胞癌组织中的表达情况,及其在上皮间质转化(EMT)中的作用。方法:用免疫组化法检测59例口腔鳞状细胞癌组织(实验组)和15例正常口腔黏膜组织(对照组)中Periostin、E-cadherin、Vimentin表达情况,分析Periostin与E-cadherin、Vimentin间相关关系。结果:59例口腔鳞状细胞癌组织中Periostin、E-cadherin、Vimentin阳性表达率分别为71.2%、52.5%、39.0%, Periostin表达与肿瘤TNM分期、分化程度、淋巴结转移密切相关(P<0.05);且Periostin与E-cadherin表达降低和Vimentin表达上调间均存在相关性(P<0.01)。结论:Periostin可能通过调控上皮间质转化促进口腔鳞状细胞癌侵袭转移。  相似文献   

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