Study Of Caveolin-1 In The Progression And Invasion Of Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma(ESCC) is one of the most common digestive malignant tumors. Recently, with the development of economy, the aging population, and the changes of people’s diet structure and environment, Esophageal carcinoma morbidity and mortality, accounting for the fourth place among all kinds of malignant tumors, increased year by year and had gradual rejuvenation trend, seriously imperilling human life. Invasion and metastasis is the main cause of poor healing and death. Nowadays, surgical operation combined with radiotherapy and chemotherapy improves the resection rate and 5 years of survival rate to some extent, but 5 years of survival rate is still less than 40%. There are no obvious symptoms in early stage of esophageal carcinoma, so patients often have been in the advanced stage, losing the best treatment period. It is necessary that the basic research related to esophageal carcinoma is engaged to provide guidance for clinical early diagnosis and overall treatment. With the deepening of molecular biology research, It is generally believed that the occurrence, development, invasion and metastasis of ESCC is the result of multi-factor, multi-stage, and multi-gene changes. From the normal esophageal mucosa, atypical hyperplasia, precancerous lesion to carcinoma of esophagus is the process of gradual evolution in which it is related to died, environment, autoimmunity and other factors, but also closely related with oncogene activation, anti oncogene inactivation, disorder of cell signal transaction system, and imbalance of cell proliferation and apoptosis.ESCC tissues were selected as the study object and Caveolin-1 protein distribution and expression in ESCC tissues were detected, meanwhile MMP-2, β-catenin protein expression which is closely correlated with invasion and metastasis were detected in order to explore the possible role of Caveolin-1 in the invasion and metastasis of extracellular matrix, find molecular markers for early diagnosis and prognosis of monitoring, and provide new ideas for clinical treatment of esophageal cancer.Objective: To explore the expression, clinical significance of Caveolin-1 protein and its correlation with MMP-2, β-catenin, and investigate its mechanisms of the action.Methods: 110 cases of ESCC tissues and 15 cases of normal esophageal mucosa tissues from department of thoracic surgery in First Affiliated Hospital of Hebei North University from June 2013 to June 2014 were selected. Cancer tissue were excised from the ESCC tissues center, and normal tissue were excised from stump of the cut edge of the specimenat. All cases were diagnosed by pathology,whthout radiotherapy, chemotherapy, biological, and immunotherapy with no other parts of primary tumor. The expression of Caveolin-1,MMP-2,and β-catenin in ESCC and normal esophageal mucosa tissues were detected by Immunohistochemical technique to investigate its correlation with the clinical pathological parameters.Results: 1 Immunohistochemical staining of Caveolin-1The positive immunohistochemical staining of Caveolin-1 protein was mainly located in the cell membrane and cytoplasm.The expression of Caveolin-1 of cell membrane and cytoplasm in normal esophageal mucosa tissue is light yellow,but in ESCC is yellow or tan with no regular arrangement.The positive expression of Caveolin-1 in ESCC was higher than that in normal esophageal tissues, and the positive expression of Caveolin-1 in ESCC and normal esophageal tissues were 73.64%(81/110) and 33.33%(5/15), and the difference was statistically significant(χ2= 5.398, P<0.05). 2 Immunohistochemical staining of MMP-2The positive immunohistochemical staining of MMP-2 protein was mainly located in the cell cytoplasm.The expression of MMP-2 of cell cytoplasm in normal esophageal mucosa tissue is colorless or light yellow,but in ESCC is pale brown with focal or diffuse distribution and different size, coloration.The positive expression rate of MMP-2 protein in esophageal carcinoma tissues was 84.55%(93/110),which was significantly higher than that in normal tissues 26.67%(4/15), and there was significant difference(χ2= 4.744,P<0.05). 3 Immunohistochemical staining of β-cateninThe positive immunohistochemical staining of Caveolin-1 protein was mainly located in the cell membrane.The expression of β-catenin of cell membrane in normal esophageal mucosa tissue is pale brown,but in cytoplasm and nucleus of ESCC is pale brown with reduced expression or loss with different degree in cell membrane.The positive expression rate of β-catenin protein in ESCC was 82.73%(91/110),which was significantly higher than that in normal tissues 20.00%(3/15), and there was significant difference(χ2= 5.33,P<0.05). 4 The correlation between Caveolin-1,MMP-2,β-catenin protein and clinical pathological parameters in ESCC 4.1 The correlation between Caveolin-1 and clinical pathological parameters in ESCCIn 110 cases of ESCC tissue,expression of Caveolin-1 in cell membrane and cytoplasm is gradually strengthened with the reduction in the degree of differentiation,the positive rate was 47.62%,70.91% and 94.11%,and the difference was significant(P<0.05);In 78 cases with lymph node metastasis,the positive expression accounted for 84.62%, while in 32 cases without lymph node metastasis, the positive expression accounted for 46.88%, and the difference was statistically significant(P<0.05);In 21 cases with liver metastasis,the positive expression accounted for 95.24%, while in 89 cases without liver metastasis, the positive expression accounted for 68.54%, and the difference was statistically significant(P<0.05);In 47 cases with III-IV stage,the positive expression accounted for 87.23%, while in 63 cases with I-II stage, the positive expression accounted for 63.49%, and the difference was statistically significant(P<0.05);The expression of Caveolin-1 protein was not correlated with the patient’s age,gender,tumor size,and the depth of tumor invasion(P>0.05).. 4.2 The correlation between MMP-2 and clinical pathological parameters in ESCCIn 110 cases of ESCC tissue,expression of MMP-2 in cell cytoplasm is gradually strengthened with the reduction in the degree of differentiation,the positive rate was 61.90% 、 87.27% and 94.12%,and the difference was statistically significant(P<0.05);In 78 cases with lymph node metastasis,the positive expression accounted for 96.15%, while in 32 cases without lymph node metastasis, the positive expression accounted for 56.25%, and the difference was statistically significant(P<0.05);In 21 cases with liver metastasis,the positive expression accounted for 100.00%, while in 89 cases without liver metastasis, the positive expression accounted for 80.09%, and the difference was statistically significant(P<0.05);In 47 cases with III-IV stage,the positive expression accounted for 93.62%, while in 63 cases with I-II stage, the positive expression accounted for 77.78%, and the difference was statistically significant(P<0.05);The expression of MMP-2 protein was not correlated with the patient’s age,gender,tumor size,and the depth of tumor invasion(P>0.05). 4.3 The correlation between β-catenin and clinical pathological parameters in ESCCIn 110 cases of ESCC tissue,ectopic expression of β-catenin in cell membrane and cytoplasm is gradually strengthened with the reduction in the degree of differentiation,the positive rate was 52.38% 、 85.45% and 97.06%,and the difference was statistically significant(P<0.05);In 78 cases with lymph node metastasis,the positive expression accounted for 94.87%, while in 32 cases without lymph node metastasis, the positive expression accounted for 53.13%, and the difference was statistically significant(P<0.05);In 21 cases with liver metastasis,the positive expression accounted for 100.00%, while in 89 cases without liver metastasis, the positive expression accounted for 78.65%, and the difference was statistically significant(P<0.05);In 47 cases with III-IV stage,the positive expression accounted for 95.74%, while in 63 cases with I-II stage, the positive expression accounted for 73.02%, and the difference was statistically significant(P<0.05);The expression of β-catenin protein was not correlated with the patient’s age,gender,tumor size,and the depth of tumor invasion(P>0.05). 5 The correlation with Caveolin-1, MMP-2, β-catenin protein in ESCCThe expression of Caveolin-1 protein in ESCC was significantly positively corelated with that of MMP-2 and β-catenin(r=0.429, P=0.000;r=0.545,P=0.000)Conclusion:1 The immunized chromonization of Caveolin-1,MMP-2,β-catenin :Caveolin-1,MMP-2,β-catenin in ESCC takes on a higher level than in a normal esophageal tissues.2 The expression of Caveolin-1, MMP-2, β-catenin protein in ESCC is positively correlated with the degree of differentiation,liver metastasis, lymph node metastasis, and TNM stage.3 The expression of Caveolin-1 protein in ESCC is significantly positively corelated with that of MMP-2 and β-catenin,and Caveolin-1 induces and promotes cancer invasion and metastasis by regulating the expression of MMP-2 and β-catenin.4 Caveolin-1 is highly relevant to incidence,development,invasion and metastasis of ESCC in different perspectives, which offer a new approach to further study of diagnosing,treatment,prevention, and monitoring transferring.