Correlation Of PTEN,E-cadherin And CD44v6 Expression With Invasion And Metastasis In Esophageal Carcinoma

Objective: Esophageal carcinoma (EC) is a kind of common diseases in ourcountry, especially in Henan province. And the disease incidence of EC has a trend ofincreasing. In some areas, specially in Henan province, it has leaped to the forth deah ofall the maligant tumors. The most cases that caused the death of esophageal carcinomaare its invasion and metastasis. Because the invasion and metastasis in esophagealcarcinoma are a complicated courses and stages of pathophysiology, and have becomeone of the most cases of affectting the life qualities and period of life time of patients,so the explore about the invasion and metastasis of esophageal carcinoma has becomea focus.It has been proved wehther or not lymphatic metastasis of EC is a major factor to theclinical prognosis. Therefore, in the process of diagnosis and therapy of EC, how to checkand control lymphatic metastasis is very important. In despite of there have been a lot ofreports about PTEN,E-cadherin and CD44v6 with the invasion and metastasis oftumor respectively, there was no report about the relation between the three genes(PTEN,E-cadherin and CD44v6) in the invasion and metastasis of esophagealcarcinoma.PTEN (phospatase and tension homology deleted from chromosome ten) was the first defined tumor suppressor gent which product acted as phosphatase and sharedextensive homology with cytosketal protein, mapping to human chromosome 10q23.3.Recently, many studies showed that there were several putative mechanisms relatingto tumor suppression such as inhibiting cell invasion and metastasis bydephosphorating FAK; increaseing cell apoptosis and inhibiting cell growth bydephosphorating PIP3; restraining cell differentiation by inhibiting MARK signalpathway. Mutation or abnormal expression of PTEN protein occurred commonly inmultiple tumors and significantly correlates with tumorigenesis and progression ofdifferent malignancies.This report only used one method that is inmmunohistochemistry, to indicatethe expressions of the PTEN,E-caderin and CD44v6 on the esophageal carcinomatissue and normal esophageal tissue. In order to explore the relations farther ofPTEN,E-caderin and CD44v6 expressions and the invasion and metastasis inesophageal carcinoma, to find the early defective markers of invasion and metastasisof esophageal carcinoma and to research the useful ways to surpress the invasion andmetastasis of esophageal carcinoma.This article detect integrally the expressions of PTEN,E-cadherin and CD44v6in different epithelial lesions, including normal, atypical hyperplasia, and invasivecarcinoma of esophageal to analyze the expressions of PTEN,E-cadherin andCD44v6 correlated with pathologic characteristics by the immunohistochemistry ways.Those results provide the basic theory to explore the invasion and metastasis ofesophageal carcinoma.Methods: 1. Immunohistochemistry was used to detect the expressions ofPTEN,E-cadherin and CD44v6 in 39 cases of whole specimen of esophagealcarcinoma with different degree epithelial lesions. In addition, several clinicpathological feature was analyzed.2. All the data were analyzed statistical with SPSS 10.0 statistic software. Thenumerable data were analyzed with x~2 test and Spearman test of correlations. Thesignificant testing standard isα=0.05.Results: 1. PTEN expression was observed in all the cases of normal esophageal tissues (39/39,100%), in the other hand, there are only 25 expressions of PTEN in39 cases of EC (P＜0.01). And the expressions of PTEN was associated with thedegree of differentiation as well as the depth of invasion, and lymph node metastasis(P＜0.05).2. There are 18 cases (18/39, 46.15%) of EC showed expressions of E-cadherin.However, there are 32 cases (32/39, 82.05%) of normal esophageal tissues showedexpressions of E-cadherin (P＜0.01). And the expressions of E-cadherin was associatedwith the degree of differentiation as well as the depth of invasion, and lymph nodemetastasis (P＜0.05).3. CD44v6 expression was observed in 12 cases (12/39, 30.77%) of normalesophageal tissues, and in 13 cases (13/23, 56.52%) of atypical hyperplasia tissue, andin 30 cases (30/39, 76.92%) of EC (P＜0.01). And the expressions of CD44v6 wasassociated with the degree of differentiation as well as the depth of invasion, andlymph node metastasis (P＜0.05).4. Both of the expressions of PTEN and E-cadherin in EC were decreased withthe decrease of differentiation degree as well as the depth of invasion, and lymphmetastasis (P＜0.05).5. The expressions of PTEN were positively with E-cadherin, and the both of theexpressions of E-cadherin and PTEN were negatively with CD44v6.6. PTEN,E-cadherin and CD44v6 were positively related to the depth ofinvasion, and lymph node metastasis of EC (P＜0.05).Conclusion: 1. The expressions of PTEN in normal esophageal squamous celltissues were higher than that in atypical hyperplasia tissues, and invasivecarcinoma, and the expressions of PTEN were reducing in the course from normal toinvasive carcinoma. And the expressions of PTEN in the EC tissues with lymphnodemetastasis were lower than that without lymphnode metastasis. It indicates that PTENgene plays an important role in carcinogenesis and progress of esophageal carcinomaand there was correlation between the expressions of PTEN protein and metastasis ofesophageal carcinoma. It also indicated that PTEN was an effective inhibitor and itprovided a new clue for preventeing tumor invasion and metastasis clinically. 2. The positive rates of the expression of E-eadherin protein were different inesophageal squamous tissues, atypical hyperplasia tissues and invasion tissue withdifferent invasion depth. The positive expression rates of E-cadhefin, from normaltissue to invasive carcinomas tissues were decreased gradually accompany with theinvasion depth and lymph node metastasis. And the protein positive expression rateswhich invaded to outer lay were lower than that invaded to low-muscle lay anddeep-muscle lay, it indicated that there was correlation between the expression ofE-cadherin protein and invasion of esophageal squamous carcinoma. E-eadherin canbe used as an important marker for predicting the metastasis potential of esophagealcarcinoma and the prognosis.3. However, The positive rates of the expression of CD44v6 protein werehigher in vasion carcinoma than normal tissue and atypical hyperplasia tissues. Andthe positive expression rates of carcinomas tissues were increased graduallyaccompany with the invasion depth and lymph node metastasis. And the proteinpositive rates which invaded to outer lay were higher than that invaded to low-musclelay and deep-muscle lay. It indicated that there was correlation between theexpressions of CD44v6 protein and invasion of esophageal carcinoma. Theoverexpression of CD44v6 promotes the invasion and metastasis of esophagealcarcinoma. CD44v6 can be used as a important marker for predicting the metastasispotential of esophageal carcinoma and the prognosis.4. The positive rate of CD44v6 was increased gradudlly with the the progress ofinvasion ang lymphatic metastasis verse PTEN and E-cadherin were decerasedgraduallly. Positive correlation was observed in EC between the PTEN andE-cadherin, and negative correlation was observed with CD44v6. These data shows acorrelation among the PTEN,E-cadherin and CD44v6 expressions and a potential ofinvasion and metastasis in EC. PTEN, E-cadherin and CD44v6 may be prognosticindicators in EC. The co-expression of PTEN,E-cadherin and CD44v6 are related tothe potential tumor proliferation, invasion and metastasis, and there is closecorrelation between these three expression. Both of the PTEN and E-cadherin act ininhibiting the invasion and metastasis of EC and CD44v6 act in promoting the invasion and metastasis of EC. The co-expression may be important to determine themalignant biological property and the prognosis of esophageal carcinoma.