The Expression Of Adrenomedullin In Epithelial Ovarian Tumors And Its Association With Microvessel Density

The morbidity of ovarian cancer accounts for the third place of femalegenital tract tumors following uterine cervical cancer and endometrial cancer.Because of the characteristics that patients are often diagnosed in advancedstages and its rapid progress,poor prognosis and high mortality, ovariancancer has become a leading cause of gynecological cancer death. So it isnecessary to search for relative factors in order to diagnose and treat thedisease when it is in early stage and give effective therapeutic methods.Adrenomedullin(ADM) is a pluripotent peptide initially isolated frompheochromocytoma ,which is found in a variety of tumor cell lines ormalignant tissues and can enhance the growth of tumor cells by several ways.1.It has the proliferative capabilities in a wide variety of cancer cells. Manystudies show ADM stimulates growth in several cancer types. ADM has beenshown to induce cAMP production in tumor cells, so it may function as agrowth regulator in tumor proliferation. The neutralizing monoclonal antibodyto ADM inhibited tumor cell growth in a dose-dependent manner, suggestingthat ADM is a novel mitogenic regulatory peptide. 2.ADM is an apoptosissurvival factor for cancer cells. ADM reduces endothelial cell apoptosis viaNO. A study has shown ADM-overexpressing malignant cells showed lowerlevels of proapoptotic factors concomitant with higher resistance to apoptosis.3.ADM helps tumor cells evade immune surveillance. More and more reportssuggest that ADM functions as an immunosuppressor factor helping cancercells to evade immune system actions. ADM enables cancers to circumventimmune surveillance by suppressing T-lymphocyte differentiation andcytotoxic function .ADM induces cAMP production in macrophages andsignificantly inhibited cytokine-induced neutrophil chemoattractant(CINC)secretion in a dose-dependent fashion, so ADM plays an important role in thedownregulation of macrophage function via a cAMP-dependent mechanism.ADM enhances the complement regulatory function of complement factor(fH)and inhibites the alternative pathway of the complement cascade and assiststumor cells circumvent complement-mediated lysis, so ADM could beindirectly acting as a tumor survival factor. 4.ADM has angiogenic function intumors. The growth,invasion and metastasis of malignant solid tumor aredepending on angiogenesis. The new blood vessels not only supply nutritionand oxygen but also carry away wastes,which profits tumors'growth andmetastasis. It was found that ADM stimulated recovery of blood flow in theischemia model by using laser Doppler perfusion imaging. Immunostainingfor CD31 showed the enhanced flow by ADM to reflect increased collateralcapillary density. Moreover, ADM can result in vasodilatation and increaseblood flow to help the growth of tumors. We performed an immunohistochemical study on paraffin-embeddedspecimens to research the relationship between ADM and microvesseldensity(MVD),clinico-pathological features in epithelial ovarian tumors.Using a polyclonal antibody of ADM and a monoclonal antibody of CD34, wedetected the expression of ADM and CD34 protein respectively in 83 cases ofepithelial ovarian tumors, including 66 malignant tumors and 17 benigntumors. The results showed ADM expressed in the malignant and benignepithelial ovarian tumors .The positive rates of ADM in the malignant andbenign tumors were respectively 69.70% and 47.18%. The former was higherthan the latter and the difference between them was statisticallysignificant(P<0.05). In epithelial ovarian cancers, the association between theexpression of ADM and the patients'age,clinical stage and histologicalsubtype was not statistically significant(P>0.05). The positive rate(95.74%) ofADM in the cases with histological grade 3 was higher than that(57.78%) inthe cases with histological grade 1~2(P<0.05). The positive rate(90.00%) ofADM in the cases with lymph node metastasis was higher than that(50.09%)in the cases without lymph node metastasis(P<0.05). The association betweenthe expression of ADM and histological grade,lymph node metastasis wasstatistically significant(P<0.05). MVD was 34.30±21.47 in 66 cases of themalignant tumors and 16.35±8.84 in 17 cases of the benign tumors. Theformer was higher than the latter and the difference between them wasstatistically significant(P<0.05). Spearman correlation between the expressionof ADM and MVD was not statistically significant(P>0.05). For recent years, clinical studies have shown ADM overexpressed inpatients'tumors. Our study showed that ADM expressed in malignant andbenign epithelial ovarian tumors, moreover, the positive rate of ADM in theformer was higher than that in the latter(P<0.05), which suggested ADMrelated to the genesis and progress of epithelial ovarian cancers. Histologicalgrade is one of the basic features that reflect tumors'biological behavior.Higher grade means poorer differentiation,wickeder biological behavior,worse prognosis and higher recurrence rate. The relationship between ADMand histological grade suggested ADM correlated with tumors'proliferativeability, and it was involved in the malignant process, furthermore it correlatedwith patients'prognosis. The positive rate of ADM in the cases with lymphnode metastasis was higher than that in the cases without lymph nodemetastasis .Lymph node metastasis is an important pathway of ovarian cancermetastasis. The presence or absence of lymph node metastasis is one of thekey factors that affect the progress and prognosis of cancer. Thus, our resultsshowed ADM related to tumors'aggravation and poor prognosis significantly.Some foreign researches show ADM has angiogenesis in tumors. Our studyshowed the correlation between the expression of ADM and MVD was notstatistically significant. We think ADM might have not the direct relationshipwith angiogenesis in tumors and it might result in vasodilatation and increaseblood flow or resist apoptosis and help tumor cells evade immune surveillanceto help the growth of tumors. The fact MVD was higher in malignant casesthan that in benign cases may be caused by vascular endothelial growthfactor(VEGF) or other angiogenic factor. In addition, our methods of theexperiment and judging decisions don't agree with others'entirely, which mayresult in our results'disagreements. In conclusion, the positive rate of ADM in the malignant epithelialovarian tumors was higher than that in the benign ones, which suggested ADMrelated to the genesis and progress of epithelial ovarian cancers. Using amonoclonal antibody to ADM might be a new pathway to treat epithelialovarian cancer. ADM expression was significantly associated with histologicalgrade and lymph node metastasis, so according to ADM expression level wecan identify high-risk patients in early stage ovarian cancer, evaluate patients'prognosis and make reasonable treating plans. The correlation between theexpression of ADM and MVD was not statistically significant. We think ADMmight have not the direct relationship with angiogenesis in tumors and it mightresult in vasodilatation and increase blood flow or resist apoptosis and help...