Prognostic and clinicopathological features of E-cadherin,α-catenin,β-catenin,γ-catenin and cyclin D_1 expression in human esophageal squamous cell carcinoma

AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, α-catenin, β-catenin, γ-catenin and cyclin D1 was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS：The reduced expression rate of E-cadherin, α-catenin, β-catenin and γ-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression ratewas 56.5%. Expression of γ-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (x^2=4.183 and x^2=5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (x^2=5.769, P<0.05). Reduced expression of E-cadherin and γ-catenin was associated with poor differentiation of tumor, reduced expression of γ-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and γ-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and inreduced expression one and were 78% and 48% in γ-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of α-catenin correlated with that of E-cadherin and β-catenin (P<0.05). CONCLUSION: The reduced expression of E-cadherin and γ-catenin, but not α-catenin, β-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.

Upregulated expression of Ezrin and invasive phenotype in malignantly transformed esophageal epithelial cells

AIM: To investigate the correlation between ezrin expression and invasive phenotype formation in malignantly transformed esophageal epithelial cells. METHODS: The experimental cell line employed in the present study was originated form the progressive induction of a human embryonic esophageal epithelial cell line (SHEE)by the E6E7 genes of human papillomavirus (HPV) type 18.The cells at the 35th passage after induction called SHEEIMM were in a state of immortalized phase and used as the control,while that of the 85th passage denominated as SHEEMT represented the status of cells that were malignantly transformed. The expression changes of ezrin and its mRNA in both cell passages were respectively analyzed by RT-PCR and Western blot. Invasive phenotype was assessed in vivo by inoculating these cells into the severe combined immunodeficient (SCID) mice via subcutaneous and intraperitoneal injection, and in vitro by inoculating them on the surface of the amnion membranes, which then was determined by light microscopy and scanning electron microscopy. RESULTS: Upregulated expression of ezrin protein and its mRNA was observed in SHEEMT compared with that in SHEEIMM cells. The SHEEMT cells inoculated in SCID mice were observed forming tumor masses in both visceral organs and soft tissues in a period of 40 days with a special propensity to invading mesentery and pancreas, but did not exhibit hepatic metastases. Pathologically, these tumor cells harboring larger nucleus, nucleolus and less cytoplasm could infiltrate and destroy adjacent tissues. In the in vitro study,the inoculated SHEEMT cells could grow in cluster on the amniotic epithelial surface and intrude into the amniotic stroma. In contrast, unrestricted growth and invasiveness were not found in SHEEIMM cells in both in vivo and in vitroexperiment. CONCLUSION: The upregulated ezrin expression is one of the important factors that are possibly associated with the invasive phenotype formation in malignantly transformed esophageal epithelial cells.

Correlation between expression of human telomerase subunits and telomerase activity in esophageal squamous cell carcinoma

AIM: To investigate telomerase activity and hTERT, TP-1 expression and their relationships in esophageal squamouscell carcinoma (ESCC).METHODS: Telomerase activity was measured in 60 ESCCtissues using telomeric repeat amplification protocol (TRAP)assay by silver staining. In situ hybridization was used for detecting hTERT and TP-lmRNA.RESULTS: The telomerase activity was detected in 83.3 % of ESCC tissues. The difference of telomerase activity was significant between well and poorly cancer differentiated lesions (P<0.05). The positive rate of telomerase activity was higher in patients with lymphatic metastasis than in patients without lymphatic metastasis. In cancer tissues hTERT mRNA expression was 75 % and TP-1 mRNA expression was 71.7 %. The expression of hTERT, TP-1 mRNA in well and poorly differentiated carcinoma was not significant. The expression of hTERT mRNA was correlated with telomerase activity, but TP-1 mRNA expression was not correlated with it.CONCLUSION: Telomerase activity and hTERT, TP-1 mRNA expression are up-regulated in ESCC. Telomerase activity in ESCC is correlated with lymphatic metastasis and cancer differentiation. Telomerase activity may be used as a prognostic marker in ESCC. hTERT mRNA expression is correlated with telomerase activity. Enhanced hTERT mRNA expression may initially comprehend the telomerase activity level, but it is less sensitive than TRAP assay.

Clinicopathologic analysis of esophageal and cardiac cancers and survey of molecular expression on tissue arrays in Chaoshan littoral of China

AIM: To investigate clinical and pathologic data of esophageal carcinoma (EC) and cardiac carcinoma (CC) among residents in Chaoshan region of China.METHODS: Clinical and pathologic data of 9 650 patients with EC and 4 173 patients with CC in the Chaoshan population were collected and analyzed. Moreover,Chaoshan esophageal carcinoma tissue arrays were made for high-throughput study.RESULTS: Male to female ratio was 3:1 in patients with EC and 4.75:1 in CC. The average age of the occurrenceof EC was 54.6 years, and of CC was 58.1 years. For both EC and CC, age at diagnosis was a little younger in Chaoshan region than in most other areas. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%); the second was the lower third (15.3%). The main gross type of esophageal carcinoma was ulcerative type (41.50%); the medullary type was the second (39.6%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer (96.4%);adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma (94.5%). Chaoshan esophageal carcinoma tissue arrays were easily for high-throughput study, and tissue cores with a diameter of 1.5 mm could better keep more structure for molecular expression study.CONCLUSION: Both EC and CC are common in males.The average occurrence age of EC and CC is younger in Chaoshan than in most other regions of China. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer; adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma. Tissue arrays technology is applicable for rapid molecular profiling of large numbers of cancers in a single experiment.