Expression of e-cadherin, alpha-catenins and Beta-catenins in human gastric carcinomas - correlation with histology and tumor progression

The expression of cell-cell adhesion molecule, E-cadherin and its associated proteins, alpha- and beta-catenins in human gastric carcinomas was examined by Western blotting. All the seven gastric carcinoma cell lines expressed E-cadherin except KATOIII, which was derived from pleural effusion of a scirrhous type stomach cancer or Borrmann's type-4 carcinoma. The expression of alpha-catenin was not detected in HSC43 derived from scirrhous carcinoma, while HSC39 expressed abnormal beta-catenin caused by genetic alteration. In gastric carcinoma cases, the levels of E-cadherin and alpha-catenin were significantly lower in poorly differentiated adenocarcinomas and scirrhous carcinomas when compared to other types of gastric carcinomas. Deeply invasive carcinomas expressed E-cadherin and alpha-catenin at lower levels. However, the expression level of alpha-catenin was not necessarily consistent with that of E-cadherin. One of 10 gastric carcinomas examined showed complete deletion of alpha-catenin gene in Southern blotting. beta-catenin was expressed at lower level in poorly differentiated adenocarcinomas than in well-differentiated adenocarcinomas. These findings suggest that reduction in the expression of E-cadherin and its associated molecules, catenins, is involved in the development and infiltrative growth of scirrhous type gastric carcinomas.     

Localization of IQGAP1 is inversely correlated with intercellular adhesion mediated by e-cadherin in gastric cancers

Down-regulation of E-cadherin function is characteristic of cancer cells and might involve the small G-protein Rho family, including Rac1 and Cdc42. IQGAP1 has been reported to be one of the target proteins of Rac1 and Cdc42. To elucidate the role of IQGAP1 in cancer-cell adhesion, its expression was investigated in 47 cases of human gastric cancer by immunohistochemistry and Western blot upon protein fractionation, especially in comparison with E-cadherin and catenin expression. In the non-cancerous columnar epithelium of the stomach, IQGAP1, as well as E-cadherin/catenin, was expressed at the cell-cell boundary. IQGAP1 was frequently observed diffusely in the cytoplasm in intestinal-type tumors (20/22 cases) but was expressed at the cell membrane in diffuse-type tumors (19/25 cases), thus showing significant association with tumor differentiation (p < 0.01). Interestingly, membranous expression of IQGAP1 was inversely correlated with that of E-cadherin (p < 0.05) or alpha-catenin (p < 0.001). These observations were consistent with the Western blot results following protein fractionation. IQGAP1 was dominantly expressed in the soluble fraction in differentiated tumors; however, in undifferentiated tumors, it was mostly in the insoluble fraction. In contrast, both E-cadherin and alpha-catenin were detected only in the insoluble fraction. Thus, subcellular localization of IQGAP1 from the cytoplasm to the cell membrane was correlated with E-cadherin dysfunction and tumor dedifferentiation in gastric carcinogenesis.     

Altered expression of E-cadherin in gastric cancer tissues and carcinomatous fluid.

Expression of E-cadherin in 21 patients with various histological types of gastric carcinomas was studied by immunoperoxidase staining. Intercellular boundaries of almost all cancer cells in well and moderately differentiated adenocarcinomas stained as deeply for E-cadherin as normal gastric mucosa. However, singly infiltrating cells of those histological types were poorly stained. In poorly differentiated adenocarcinomas, cancer cells forming clusters stained lightly and those infiltrating singly stained even less. In signet ring cell carcinomas, hardly any staining was observed. In each histological type, the staining patterns and intensity at different layers of the gastric wall, were essentially the same. Cancer cells from carcinomatous ascites of gastric adenocarcinomas and pancreatic adenocarcinomas, and those from pleural effusion of lung adenocarcinomas were also studied by immunofluorescence staining. Of 11 specimens, ten were negative and only one from a lung adenocarcinomas was positively stained. By phase-contrast microscopic observations, none of these cancer cells including those from the lung adenocarcinomas, formed obvious cell-cell contacts. Cell aggregation assays confirmed the above results. The molecular weight of E-cadherin of cancer cells of lung adenocarcinomas was less than intact E-cadherin as revealed by Western blot analysis. These results suggest that depressed expression and/or impaired function of E-cadherin in cancer cells, facilitates their liberation from primary sites to infiltrate freely into tissue or fluid.     

Frequent loss of E-cadherin and/or catenins in intrabronchial lesions during carcinogenesis of the bronchial epithelium

Inactivation of the cadherin-mediated cell-cell adhesion system is believed to play a role in the initial steps of cancer invasion and metastasis. Expression of E-cadherin and its intracytoplasmic binding molecules (alpha-catenin, beta-catenin, and plakoglobin) was examined immunohistochemically in 84 cases of intrabronchial precancerous lesions (bronchial squamous metaplasia (BSM) without atypia, BSM with atypia, dysplasia), and 21 cases of carcinoma in situ, and 4 cases of microinvasion to the bronchial wall, and 32 cases of stage I well differentiated squamous cell carcinoma (squamous cell carcinoma) to investigate the association between expression of E-cadherin and/or catenins and cancer progression. Reduced expression of E-cadherin and/or catenins was closely correlated with an atypical grade of dysplasia in the basal layer (p<0.05). In particular, downregulation of E-cadherin and/or catenins was associated with an atypical grade of BSM with atypia in intrabronchial lesions (p<0.01). We conclude that downregulation of alpha-catenin and/or beta-catenin, which may reflect dysfunction of the cadherin-mediated cell-cell adhesion system, is an important marker for atypical grade during carcinogenesis of the bronchial epithelium.     

Involvement of nectin in the localization of IQGAP1 at the cell-cell adhesion sites through the actin cytoskeleton in Madin-Darby canine kidney cells

IQGAP1, a putative downstream target of the Rho family small G proteins, Cdc42 and Rac, localizes at adherens junctions (AJs) in epithelial cells. It has been suggested that IQGAP1 localizes at AJs through its binding to beta-catenin, and negatively regulates the E-cadherin-mediated cell-cell adhesion. Nectin is a Ca(2+)-independent, immunoglobulin-like cell-cell adhesion molecule that localizes at AJs. Nectin is associated with E-cadherin through their respective cytoplasmic tail-binding proteins, afadin and catenins, and involved in the formation of AJs cooperatively with E-cadherin. Here we investigated a role of nectin in the localization of IQGAP1 at AJs. Ca(2+) chelation from the medium causes disruption of the E-cadherin-mediated cell-cell adhesion, but not the nectin-based cell-cell adhesion, in Madin-Darby canine kidney (MDCK) cells. IQGAP1 remained at the residual nectin-based cell-cell adhesion sites where the E-cadherin immunofluorescence signal disappeared. Restoration of Ca(2+) in the medium causes re-accumulation of E-cadherin to the residual nectin-based cell-cell adhesion sites to re-form AJs. Nectin inhibitors inhibit this re-accumulation of E-cadherin to re-form AJs by impairing the nectin-based cell-cell adhesion. The nectin inhibitors also reduced the localization of IQGAP1 at the cell-cell adhesion sites. When MDCK cells were incubated with microbeads coated with the extracellular fragment of nectin that interacts with cellular nectin, IQGAP1 also accumulated at the bead-MDCK cell contact sites. The accumulation of IQGAP1 at the cell-cell adhesion sites was inhibited by actin filament-disrupting agents, latrunculin A and cytochalasin D. These results indicate that nectin is involved in the localization of IQGAP1 at AJs through the actin cytoskeleton.     

Decreased expression of CD44, alpha-catenin, and deleted colon carcinoma and altered expression of beta-catenin in ulcerative colitis-associated dysplasia and carcinoma, as compared with sporadic colon neoplasms

BACKGROUND: To clarify the cell adhesion status in ulcerative colitis (UC)-associated colon neoplasm, expression of cell adhesion molecules were investigated and compared with that of sporadic colon neoplasm. METHODS: A total of 14 low grade dysplasias, 16 high grade dysplasias, and 8 adenocarcinomas associated with UC and 17 sporadic adenomas with mild to moderate dysplasia, 22 adenomas with severe dysplasia, and 15 invasive adenocarcinomas were immunohistochemically examined using monoclonal antibodies against CD44, E-cadherin, alpha- and beta-catenin, and deleted colon carcinoma (DCC). RESULTS: CD44, especially its standard form, and DCC expression was stronger in the sporadic colon neoplasms than in the UC-associated lesions. Although E-cadherin did not show significant differences between the two cases, alpha-catenin was more expressed in sporadic colon adenomas with severe dysplasia and carcinomas than in their UC-associated counterparts. Membranous beta-catenin staining was stronger in UC-associated neoplasms, whereas sporadic lesions had greater cytoplasmic and nuclear expression. CONCLUSIONS: The differences in cell adhesion molecule expression suggests that UC-associated and sporadic colon neoplasms arise from different pathways of tumorigenesis.     

Alpha-catenin expression has prognostic value in local and locally advanced prostate cancer.

Normally functioning cell-cell adhesion plays an important role in the maintenance of tissue architecture and cell cohesion. E-cadherin is an important adhesion molecule of epithelial cells. In many types of cancer the expression of E-cadherin is reduced leading to increased risk of disease progression. alpha-Catenin is one of the intracellular elements of the E-cadherin-catenin complex. The abnormalities in the expression of alpha-catenin seem to associate with malignant cellular features and disease progression in prostate cancer. To further analyse the significance of alpha-catenin expression, we studied 215 cases of prostate cancer by immunohistochemistry and the results were related to other known prognostic factors and patient survival during a mean follow-up period of 13 years. alpha-Catenin expression was down-regulated in 19% of the cases and 3% of the tumours were totally alpha-catenin-negative. The abnormal alpha-catenin expression and cytoplasmic signal were significantly linked with high T-category, metastatic disease, high Gleason score, perineural growth, high mitotic rate, high S phase fraction and DNA aneuploidy (P < 0.05 for all). In the survival analysis, reduced alpha-catenin expression (P = 0.06) and cytoplasmic signal (P = 0.04) were related to unfavourable patient outcome. In the multivariate analysis, including TM-classification and Gleason score, alpha-catenin expression had independent prognostic value in T1-2 M0 tumors. In the M0 tumours, abnormal alpha-catenin signal was independently associated with recurrence-free survival as well. The results indicate that down-regulation of alpha-catenin is related to several malignant cellular features, and it seems to have prognostic significance in the early phases of cancer progression. We suggest that alpha-catenin expression can provide prognostic information in early prostate cancer.     

Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases.

Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease. In this study, changes in the expression of the components of the E-cadherin-catenin cell adhesion complex have been investigated using immunohistochemical techniques in primary tumours and nodal metastases from 36 patients with squamous cell carcinoma of the head and neck. For 14 patients the corresponding primary and nodal metastases samples were available. None of the 51 samples showed normal E-cadherin expression when compared with either the adjacent normal squamous epithelium or with normal colonic epithelium that was used as positive control material. In 88% of primary tumours fewer than 50% of cells exhibited normal membranous E-cadherin expression. Loss of membranous E-cadherin expression was more extensive in poorly differentiated carcinomas while, in individual carcinomas, membranous E-cadherin expression was stronger in those parts of the neoplasm that expressed the differentiation marker involucrin. Expression of beta-catenin generally paralleled that of E-cadherin, but in 12 cases there was strong membranous beta-catenin expression in samples that exhibited predominantly cytoplasmic E-cadherin labelling. Expression of alpha-catenin was generally weak and did not correlate with the expression of either beta-catenin or E-cadherin. Marked intratumoral heterogeneity for protein expression was evident for all antibodies, and the abnormal expression of the catenins is a novel finding. E-cadherin is expressed more intensely in cells with greater squamous differentiation, but there was no correlation between the decreased expression of any of the adhesion molecules of the E-cadherin complex tested and local recurrence, metastasis or survival. The loss of expression of components of the E-cadherin complex is a common abnormality in squamous carcinomas and, while it may be permissive for metastasis, it does not appear to be the only determinant of this process.     

Expression pattern of the scaffold protein IQGAP1 in lung cancer

IQGAP1 is a scaffold protein whose function relates to signal transduction, cell adhesion, local invasion, and distant metastasis of cancer cells. We examined the expression patterns of this protein and clinicopathologic features of lung cancer, and the antibody against IQGAP1 was used for immunohistochemical analysis. Of the 70 surgical specimens examined, there were 40 adenocarcinomas, 19 squamous cell carcinomas, 5 large cell carcinomas, 3 small cell carcinomas, 2 carcinoid tumors, and 1 mucoepidermoid carcinoma. The localization of IQGAP1 was classified into three types: 1) cytoplasmic, 2) membranous, and 3) reduced expression. In adenocarcinoma, the 3 types were observed equally, and differentiation grade was related to the expression pattern. The cytoplasmic type was common in well-differentiated adenocarcinomas, and membranous or reduced expression was frequently seen in moderately- or poorly-differentiated adenocarcinomas. In squamous cell carcinoma, the membranous type was most common. Although the staining pattern of IQGAP1 did not correlate with the positivity of regional lymph nodes, survival in those patients with a cytoplasmic type was significantly better than others with adenocarcinoma (p=0.0144). Expression typing of IQGAP1 in lung cancer was associated with histologic type and can be used to predict survival in patients with adenocarcinoma of the lung.     

Abnormal expression of the E-cadherin-catenin complex in dysplastic Barrett's oesophagus

It is now accepted that altered E-cadherin-catenin complex expression in oesophageal cancer correlates with clinical and pathological parameters, while abnormal E-cadherin expression occurs early in Barrett's oesophagus. We evaluated immunohistochemically the expression and cellular localization of alpha-, beta-, and gamma-catenin, and E-cadherin in 5 dysplastic and 26 non-dysplastic cases of Barrett's oesophagus. Usually all three catenins were localized at the cell membrane, as was E-cadherin. A similar staining pattern for E-cadherin and the catenins was observed in all cases of non-dysplastic Barrett's syndrome. However, 60% (3/5) of cases with dysplasia showed loss of membranous beta-catenin staining and diffuse cytoplasmic distribution, with predominantly nuclear localization in two cases. Membranous staining and concomitant cytoplasmic localization of E-cadherin, alpha-catenin and gamma-catenin were seen in one case with abnormal beta-catenin immunoreactivity. Our results indicate that altered subcellular distribution of beta-catenin occurs frequently in dysplastic Barrett's oesophagus and possibly reflects the signalling function of this molecule.     

Alpha-catenin is required for IGF-I-induced cellular migration but not invasion in human colonic cancer cells

The mechanisms by which growth factors cooperate with cell adhesion molecules to modulate epithelial cell motility remain poorly understood. Here, we investigated the role of the E-cadherin/catenin complex in insulin-like growth factor (IGF-I)-dependent cell migration and invasion. We used variants of the HCT-8 colon cancer family that differ in their expression of alphaE-catenin, an intracellular molecule that links the E-cadherin/catenin complex to the actin cytoskeleton. Migration was determined using a monolayer wound model and cell invasion by the penetration of the cells into type-I collagen gels. We showed that alpha-catenin-deficient cells were not able to migrate in cohort upon IGF-I stimulation. Transfection of these cells with alpha-catenin isoforms (alphaN- or alphaT-catenin) restored migratory response IGF-I. These results suggest that alpha-catenins are involved in the signal issued from the E-cadherin/catenin complex to regulate IGF-I-stimulated migration. In contrast, IGF-I promoted invasion of both alpha-catenin-deficient and alpha-catenin-expressing cells, indicating that alpha-catenin did not participate in the regulation of IGF-I-induced invasion. Inhibition of E-cadherin function by treatment with MB-2 monoclonal antibodies inhibited both IGF-I-dependent cell migration and invasion. Taken together, our results indicate that functional alpha-catenin is essential for migration but not for invasion, while E-cadherin is involved in both phenomena.     

Aberrant expression and phosphorylation of beta-catenin in human colorectal cancer.

The cytoplasmic domain of cadherins is known to associate with the intracellular proteins, catenins, which link cadherins to the actin-based cytoskeleton. In this study, we immunohistochemically investigated the expression of beta-catenin as well as E-cadherin and alpha-catenin in 86 human colorectal cancers, and we analysed their coexpression pattern and relationship to clinicopathological factors. In cancerous tissues, the frequency of reduced expression of beta-catenin (28 of 86, 33%) was similar to that of E-cadherin (19 of 86, 22%), but less than that of alpha-catenin (47 of 86, 55%). All three molecules were expressed strongly, as was the normal epithelium, in 36 cases (42%), whereas the rest (50 cases, 58%) showed reduction in one of the molecules. The reduction of beta-catenin expression was significantly correlated with dedifferentiation, Duke''s stage, lymph node metastasis and liver metastasis. Next, we examined tyrosine phosphorylation in the protein complex immunoprecipitated with E-cadherin, as E-cadherin function is down-regulated by receptor-type tyrosine kinase in vitro. It was of interest that up-regulation of tyrosine phosphorylation of beta-catenin was more frequently observed in cancerous tissues than in the matching normal mucosa. These results suggest that beta-catenin may have important regulatory roles within an E-cadherin-mediated adhesion system in human colorectal cancers.     

Expression of adhesion molecules and transforming growth factor-β in pleomorphic carcinomas of the lung

Pleomorphic carcinoma (PC) of the lung consists of an epithelial component showing the histology of poorly differentiated non-small cell carcinoma of the lung and a sarcomatous component, that is more aggressive compared to non-small cell carcinoma of the lung. To determine the differences between an epithelial component of PC and poorly differentiated non-small cell carcinoma, the expression of adhesion molecules (E-cadherin, β-catenin and N-cadherin) and transforming growth factor-β (TGF-β) was compared immunohistochemically among 14 poorly differentiated adenocarcinomas of the lung (PDAs) and 14 PCs of the lung, with an epithelial component, showing the histology of PDA. Expression levels of E-cadherin and β-catenin were significantly lower in epithelial or sarcomatous components of PCs than in PDAs while that of TGF-β was significantly higher in epithelial components of PCs than in PDAs. No significant difference was found in incidences of the expression of these molecules between epithelial and sarcomatous components of PCs. No significant difference was noted in the expression level of N-cadherin among PDAs and epithelial and sarcomatous components of PCs. The present results showed that E-cadherin and β-catenin expression is reduced and TGF-β expression is increased in epithelial components of PCs with the same histology as PDA when compared to PDAs, suggesting that an epithelial component of PC is distinct from non-small cell carcinoma with the same histology.     

Induction of Glandular Stomach Cancers in C3H Mice Treated with N-Methyl-N-nitrosourea in the Drinking Water

Establishment of an animal model of stomach carcinogenesis in mice was attempted using N-methyl-N-nitrosourea (MNU) in the drinking water. One hundred and forty-eight male 6-week-old C3H mice were given MNU in their drinking water at a concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks. At the end of this time, dose-related induction of adenomatous hyperplasias was found. From weeks 31 to 54 adenocarcinomas developed in a dose-dependent manner in groups 1, 2 and 3. In total, 6 well differentiated and 5 poorly differentiated adenocarcinomas as well as 6 signet ring cell carcinomas arose in 15 stomach cancer-bearing animals in group 1, 4 well differentiated and 2 poorly differentiated adenocarcinomas with one signet ring cell carcinoma in 5 mice of group 2 and one well differentiated adenocarcinoma in group 3. In the forestomach, only one squamous cell carcinoma was found at week 54 in group 1 along with a single well differentiated adenocarcinoma in the duodenum. Thus, MNU in the drinking water selectively induced neoplastic lesions in the glandular stomach epithelium of mice.     

Overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters in ovarian carcinomas

IQGAP1 is a multifunctional protein involved in actin cytoskeleton assembly and E-cadherin-mediated cell adhesion. To determine the role of IQGAP1 in ovarian tumors, we evaluated IQGAP1 expression by immunohistochemistry in 17 adenomas, 30 borderline tumors and 80 adenocarcinomas and its relation with patient survival. IQGAP1 was overexpressed in adenocarcinomas compared with adenomas and borderline tumors. Enhanced immunostaining in invasive tumor fronts was categorized as focal or diffuse. The diffuse expression pattern correlated with high histological grade and clinicopathological stages. IQGAP1 overexpression and diffuse invasion pattern were significantly associated with poor prognosis by multivariate analysis. Our findings suggest the involvement of IQGAP1 in the progression and spread of ovarian adenocarcinomas. Overexpression and diffuse expression pattern of IQGAP1 are potentially useful independent molecular predictors of highly aggressive ovarian carcinomas.     

Dysfunction of the E-cadherin/catenin cell adhesion cascade in epithelial cancers (Review)

The E-cadherin/catenin complex is the major adhesion system that maintains the intercellular contacts in all epithelial cells. E-cadherin mediates Ca++-dependent, homotypic cell-cell adhesion and associates with the cytoskeleton through the interaction with three cytoplasmic proteins, called catenins. Dysfunction of the E-cadherin/catenin complex occurs frequently in the epithelial cancers and is correlated with dedifferentiation, advanced stage and poor prognosis. Additionally, loss of E-cadherin and alpha-catenin expression in epithelial cells in vitro, is associated with fibroblastic morphology and increased invasiveness. E-cadherin and alpha-catenin might be regarded as tumor suppressor molecules with potential diagnostic and prognostic value in epithelial cancers.     

alpha-catenin is a significant prognostic factor than E-cadherin in esophageal squamous cell carcinoma

BACKGROUND AND OBJECTIVES: The purpose of the present study was to analyze clinicopathologic variables in esophageal squamous cell carcinoma (ESCC) according to expression of E-cadherin and alpha-catenin which play an important role in cell adhesion. METHODS: We immunohistochemically examined E-cadherin and alpha-catenin in 205 patients with ESCC. The expression results were classified into two groups: preserved expression (+) and reduced expression (-). RESULTS: The incidence of E-cadherin (-) and alpha-catenin (-) was 52% and 54%, respectively and significantly related each other. For both E-cadherin and alpha-catenin, reduced expression was significantly related to tumor depth, nodal metastasis, stage, recurrence, and prognosis. In the E-cadherin (+) group, the alpha-catenin (+) and alpha-catenin (-) patients differed significantly in tumor depth, nodal metastasis, stage, hematogenous and lymphatic recurrences (P < 0.001, <0.001, <0.001, <0.001 and =0.007, respectively). According to coexpression of E-cadherin and alpha-catenin, the prognosis was best in patients with E-cadherin (+) and alpha-catenin (+), and worst in patients with E-cadherin (-) and alpha-catenin (-). Multivariate analysis revealed that alpha-catenin expression was an independent prognostic factor. CONCLUSIONS: The examination of expression of E-cadherin and especially alpha-catenin is useful for predicting lymph node metastasis and clinical outcome of ESCC.     

Clinical significance of E-cadherin-catenin complex expression in metastatic foci of colorectal carcinoma.

BACKGROUND AND OBJECTIVES: Reduced expressions of cell adhesion molecules (E-cadherin, alpha-catenin, and beta-catenin) has been reported to be associated with tumor metastasis. However, the clinical significance of such adhesion molecules in the metastatic foci remains unclear. In this study, we evaluated the prognostic significance of E-cadherin, alpha-catenin, and beta-catenin expressions in the metastatic foci of patients with colorectal carcinoma. METHODS: The expressions of E-cadherin, alpha-catenin, and beta-catenin were detected immunohistochemically in 105 primary tumors, in 30 metastatic lymph nodes, and 13 metastatic liver tumors from consecutive patients with colorectal carcinoma. RESULTS: Reduced normal expression of E-cadherin, alpha-catenin, and beta-catenin in comparison with normal epithelium was detected in 78 primary tumors, respectively. Patients who had tumors with reduced expression of adhesion molecules showed unfavorable prognosis and the reduced expression of adhesion molecules was detected as one of the independent prognostic factors for patients with colorectal carcinoma. In 30 patients with lymph node metastasis, the increased expression of adhesion molecules in metastatic lymph nodes compared with primary tumors was detected in 13 patients. The prognosis of these 13 patients was poorer than that of remaining 17 patients (P = 0.0296). Also, in 13 patients with liver metastasis, even no significant difference was observed, the mean survival time of 6 patients who had metastatic liver tumors with increased expression of adhesion molecules (10 months) was shorter than that of the remaining 7 patients (16 months; P = 0.1718). CONCLUSIONS: These results suggest that increased expression of the cadherin-catenin cell-cell adhesion system in metastatic foci may play an important role in progression of metastatic colorectal carcinomas.     

Expression of E-cadherin,alpha-catenin,and beta-catenin in the process of lymph node metastasis in oral squamous cell carcinoma

Regional lymph node metastasis is a very important prognostic indicator. In the metastatic process, reduction in cell to cell adhesion including E-cadherin-catenin cell adhesion complex is an essential step. We investigated immunohistochemical expression of E-cadherin, alpha-catenin and beta-catenin in 159 tissue samples from patients with oral squamous cell carcinoma and examined the correlation between their expressions and the presence of regional lymph node metastasis. Significantly greater reduction in expression levels of E-cadherin, alpha-catenin and beta-catenin was found in the metastatic group (n=64) compared to the nonmetastatic group (n=95) (P=0.007, 0.001, 0.001, respectively). However, there was no significant correlation between their expressions and the features of the regional metastasis, the number of metastatic lymph nodes or the presence of extracapsular metastasis. These data suggest that evaluation of the immunohistochemical expression of E-cadherin, alpha-catenin and beta-catenin is extremely valuable for the diagnosis of metastatic occurrence.