| Background and ObjectiveOvarian cancer is one of the three female genital malignant tumors and the incidence has been rising in recent years. Due to the deep location of ovary, there are no obvious early symptoms and signs. Ovarian cancer is easy to transfer and wildly spread,75% patients are diagnosed when they are in the late morbid phase.5-year survival rate is about 30%. The mortality is very high, ranking first in gynecological malignancies. In recent years, the mechanism of invasion and metastasis in ovarian cancer has become a hotspot. Therefore, if we do further study about the mechanism of invasion and metastasis of ovarian cancer and find something to inhibit the invasion and metastasis, it will be a great guide to clinical treatment.Water channel proteins (Aquaporin, AQPs) are a group of transmembrane proteins which transport water, including AQPO-AQP12, which can significantly increase the membrane permeability of water, mainly involved in the secretion and absorption of water molecules and other small molecules and the membrane stability. AQP is a kind of glycoprotein whose molecular weight is about 30ku. According to permeability differences to water and other solute, AQPs can be divided into two subfamilies:AQP3, AQP7, AQP9, AQP 10 are the same subfamily, the others are another subtribe. The former have relatively selected on the water permeability, that is, except the transport of water and glycerol also transport urea; the later only allows water molecules to pass through and has a high degree of specificity in transporting water. Recent studies have found that the water channel proteins are expression in various tumor tissues, the amount of the water channel protein has changed and cancerous cells need more quick transmembrance of water molecules than normal cells. AQPs may promote tumor angiogenesis and tumorous cell migration, involved in tumor proliferation and metastasis. Another study suggests that AQPs may be carcinogenic. The ectopic expression of water channel protein cDNA can cause changes of many phenotype, including enhanced cell proliferation, independent-proliferation growth cell fixing and so on. The research of the relationship between the development of cancers and water channel proteins has already attracted wide attention. Recently the research about the relationship between AQPSs and ovarian cancer is quite few, only including the report about AQP1, AQP3, AQP5 in epithelial ovarian tumours, and yet there is no report about the relationship between AQP4 and the development of ovarian epithelial tumors. In this study, immunohistochemistry and in situ hybridization are used to detect distributions and expressions of AQP4,5 protein and mRNA in primary epithelial ovarian tumors, and analyze the relationship about expressions of AQP4,5 protein and mRNA with clinicopathological parameters in epithelial ovarian cancer and the correlation of expressions of AQP4,5 protein and mRNA in epithelial ovarian cancer. Thus we can explore the significance of aquaporin 4,5 in the development and metastasis of epithelial ovarian cancer.Materials and methods1 Case information A surgical specimens collection of the Third Affiliated Hospital of Zhengzhou University from January,2006 to December,2009. Case specimens were stained by routine HE and dialoged by the hospital pathological researchers. In the 90 cases specimens,10 cases are normal ovarian tissues; 15 cases are benign ovarian tumors; 15 cases are ovarian borderline tumors and 50 cases are epithelial ovarian cancer (28 cases of serous adenocarcinoma; 15 cases of endometrial cancer and 7 cases of mucinous cystadenocarcinoma). The oldest patient is 80 years old. The youngest is 18 years old and the average is 47.12±6.59 years old. according to the clinical stage of ovarian cancer FIGO (2000),8 cases are stageⅠ, 10 cases are stageⅡ,23 cases are stageⅢ,9 cases are stage IV. According to histological grade (WHO 2003) of standards, there are 13 cases of well differentiation,18 cases of moderate differentiation,19 cases of poorly differentiation, 29 cases with lymph node metastasis,21 cases without lymph node metastasis; patients with ascites are 34 cases, without ascites are 16 cases. All patients did not receive any chemotherapy, radiotherapy and immunotherapy. The clinical and pathological information is complete.2 Experimental method Immunohistochemical SP method and in situ hybridization are used to detect expressions of AQP4,5 protein and mRNA in 80 cases of primary ovarian epithelial tumors and 10 cases of normal ovarian tissues and analyze the relationship about expressions of AQP4,5 protein and mRNA with clinicopathological parameters in epithelial ovarian cancer and the correlation of expressions of AQP4,5 protein and mRNA in epithelial ovarian cancer.3 Statistical analysis The data were analyzed by statistics software SPSS 16.0 package. Multi-samples rate comparison use contingency table chi-square test, rank-sum test, Fisher exact test and two sampiles rate used fourfold table chi-square test. Spaearman rank correlation analysis was used to analyze the relevance.The test standard was a=0.05. P<0.05 was considered statistically significant.Results1 Expressions of AQP4 and AQP5 proteins in epithelial ovarian tumors Positive expressions of AQP4 and AQP5 proteins in ovarian epithelial tumors are gradual rise, the positive expression rates were 26.7%(4/15) and 33.3%(5/15)in benign tumours,60.0%(9/15) and 73.3%(11/15) in borderline tumours,76.0% (38/50) and 84.0%(42/50) in malignant tumours, but positive expressions of AQP4 and AQP5 proteins in normal ovarian tissues were lower, rates were 10.0%(1/10) and 20.0%(2/10). The overall difference was statistically significant (AQP4:X2= 23.382; AQP5:X2=24.105, P<0.01); Expressions of AQP4 and AQP5 protein in epithelial ovarian cancer were significantly higher than expressions in normal ovarian tissues, the difference was statistically significant. (AQP4:X2=13.187; AQP5: X2= 14.335, P<0.01).2 Expressions of AQP4 and AQP5 mRNA in epithelial ovarian tumors Positive expressions of AQP4 and AQP5 mRNA in ovarian epithelial tumors are gradual rise, the positive expression rates were 40.0%(6/15) and 46.7%(7/15) in borderline tumours,54.0%(27/50) and 66.0%(33/50) in malignant tumours; and positive rates in benign and normal ovarian tissues were zero, the overall difference was statistically significance (AQP4:X2=29.104; AQP5:X2=38.822, P<0.01); Expressions of AQP4 and AQP5 mRNA in epithelial ovarian cancer were significantly higher than expressions in normal ovarian tissues, the difference was statistically significant. (AQP4:X2=13.582; AQP5:X2=17.202, P<0.01).3 The relationship about expressions of AQP4 protein and mRNA with clinicopathological parameters in epithelial ovarian cancer Expressions of AQP4 protein and mRNA in epithelial ovarian cancer were quite consistent. Positive expression in ovarian cancer of stageⅢ,Ⅳwere higher than the expression of stageⅠ,Ⅱ. Their comparable difference had statistic meaning(AQP4-protein:X2=4.813, AQP4-mRNA:X2=4.836, P<0.05); expressions of AQP4 in cancer with lymph node metastasis were higher than in the cancer without lymph node metastasis, the difference was statistically significant (AQP4-protein:X2= 3.944, AQP4-mRNA:X26.226, P<0.05); Positive expressions in ovarian cancer of moderate, poorly differentiation were higher than expressions of well differentiation, the difference was statistically significant (AQP4-protein:X2=6.511, AQP4-mRNA:X2=6.763, P<0.05); expressions of AQP4 in patients with ascites were higher than patients without ascites, the difference was statistically significant (AQP4-protein:X2= 6.750, AQP4-mRNA:X2=7.966, P<0.05); expressions of AQP4 were not statistically different in various pathological types of cancer (P>0.05)4 The relationship about expressions of AQP5 protein and mRNA with clinicopathological parameters in epithelial ovarian cancer Expressions of AQP5 protein and mRNA in epithelial ovarian cancer were quite consistent. Positive expressions in ovarian cancer of moderate, poorly differentiation were higher than expressions of well differentiation, the difference was statistically significant (AQP5-protein:X2=4.530, AQP4-mRNA:X2=7.711, P<0.05); expressions of AQP5 in patients with ascites were higher than patients without ascites, the difference was statistically significant (AQP5-protein:χ2=5.911, AQP5-mRNA:χ2=8.517, P<0.05); expressions of AQP5 in the clinical stage, pathological type, lymph node metastasis groups were no statistics meaning (P>0.05)5 The correlation of expressions of AQP4, AQP5 protein and mRNA in epithelial ovarian cancer Expressions of AQP4 protein and AQP5 protein, AQP4 mRNA and AQP5 mRNA in epithelial ovarian cancer were correlated (r=0.366, 0.334, P<0.05).Conclusion1 Expressions of AQP4,5 were higher in epithelial ovarian cancer, providing more water molecule channels for tumourous cells, and might be involved in the development, invasion, and metastasis of epithelial ovarian cancer.2 Expressions of AQP4,5 in patients with ascites were higher than patients without ascites, suggesting that AQP4,5 may be involved in the formation of ascites in epithelial ovarian cancer.3 AQP4 and AQP5 may be synergistic, and jointly promote the development and invasive metastasis of epithelial ovarian cancer. |
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