| [Background]With the development and application of B ultrasound, CT, MRI and other imaging technology,the detection rate of primary adrenal tumor was raised.Adrenal tumors have been considered to be one of the most common human tumors and are more and more valued by clinicians.Benign adrenal tumors often have endocrine function, excessive adrenal hormones secreted by tumor which cause the body’s endocrine dysfunction, such as hypertension, Cushing syndrome, obesity.In a short-term,it can cause serious damage to the cardiovascular such as cardiac hypertrophy, cerebrovascular accident, coronary heart disease, etc.Most of malignant adrenal tumors have endocrine function and similar clinical manifestations with benign adrenal tumors.In addition, it also performances of androphany effemination, and paraneoplastic syndrome.Although most adrenal tumors are benign tumors, malignant adrenal tumors must not be neglected by clinicians, it do more harm to human body than the benign adrenal tumors.Prognosis of adrenal benign and malignant tumors vary widely, benign tumors can be cured by surgery, while malignant tumors are often prone to recurrence and metastasis.Adrenal malignancies often express a variety of chemotherapy drug resistance gene,thus,the effect of chemotherapy and radiotherapy is poorly. Patients receive radiotherapy and chemotherapy treatment which have no effect on improve their survival rate and the main treatment for adrenal malignancies is surgical resection. Adrenal benign and malignant tumors have the similar clinical manifestations in early,so,it is difficult to differential diagnosis adrenal benign and malignant.Organizational structure and morphology of the adrenal cortical carcinoma and normal adrenal cortex are similar, it is difficult to identify in pathology.Sometimes,we should combine clinical manifestations, general specimens, endoscopic histologic features with immunohistochemical to judgment.30%to85%of the adrenal cortex cancer had distant metastasis when it was diagnosed,and distant metastasis rate was even higher in patients with non-functional adrenal cortical carcinoma. Many patients have lost the chance of operation when they were diagnosed.Compared to adrenal cortical carcinoma,it is more difficult to diagnosis of malignant adrenal pheochromocytoma.benign and malignant pheochromocytoma can not be distinguish by routine pathological examination,only the metastatic lesions were diagnosed, could the malignant pheochromocytoma be diagnosed.Therefore,dentification of adrenal benign and malignant tumors early and treatment of adrenal malignancy have positive effect on improvement of the prognosis of cancer patients.Benign and malignant adrenal tumors are difficult to differentiate in imaging and histology,so it is necessary tothe study of adrenal tumors at the molecular level,to explore its biological behavior.and offer a theoretical basis for clinical diagnosis, treatment and estimating prognosis.Gap junction (gap junction, GJ) commonly found in vertebrates, it is one of a cell connection.the gap junction protein in the adjacent cell membranes constitute of the GJ.Cx43is the first to be cloned Cx. To date, the connexin gene family comprises 20members in the mouse and21members in the human genome,19of which can be grouped as sequence-orthologous pairs.Connexins expression in the body of various organizations, such as cardiac, vascular, endocrine, exocrine glands, muscle, nerve tissue, etc. However, the expression of Cx distribution will changed in state of the different stimulation and pathological.Various compounds up to a molecular mass of1000Da can be exchanged by passive diffusion through gap junctional conduits, i.e. metabolites, ions, second messengers,nutrients, metabolites, water and electrical impulses.Gap junction mediated Gap Junction Intercellular Communication (GJIC) play an important role in regulating the cell metabolism, homeostasis, proliferation and differentiation and other physiological processes.Gap junctions within the different organizations have different functions,and it’s functionality can be divided into two aspects:GJIC-independent functions and GJIC-dependent functions,The former is Cx monomer (unpaired); the latter is the formation of two cells or more adjacent cells in Cx monomer coupling GJIC.The study confirmed that connexins function include the following aspects:①electrical coupling effect:electrical signals transmit between adjacent cells, promoting the occurrence of the action potential.②cell channel effect:ions,nutrients, fluids, metabolites can be quickly exchanged between adjacent cells,③regulation of cell growth and differentiation, participating in cell adhesion and movement, and be concerned with tumor occurrence and development of metastasis.④During the periods of embryo growth, regulating the transmission of signals between cells. Cx gene mutations is Closely related to many human diseases, such as cardiovascular disease, neurological diseases, congenital deafness, and various skin diseases.A variety of experimental methods such as electron microscopy, immunohistochemistry, Western blot, PCR,were used to study and found that there is abnormal expression of connexin and gap junctional intercellular communication defect in many human malignancies. Transfected connexin gene to target cell makeing connexin expression and recovering gap junctional intercellular communication can inhibit tumor growth or even reverse the malignant tumors,so the connexin gene was consider to be tumor suppressor genes.The study confirmed that the gap connexins expression abnormalities was associated with tumor proliferation, invasion and metastasis.However,gap junction protein express in primary adrenal tumor was rarely reported in domestic,studying connexins in adrenal tumor,exploring its relationship with tumor biological characteristics will be contribute to identify adrenal gland benign and malignant tumors.Besides, A new approach for the treatment of adrenal malignancies may provided by this study.[objective]1.To study the expressions of the gap junction protein26,32and43in primary adrenal tumors.2.To study the relationship of gap junction protein26,32and43in primary adreanl tumors.3.To investigate the value of gap junction protein26,32and43in Clinical diagnosis and prognosis assessment for primary adrenal tumors.[Content and method]The91cases typical primary adrenal tumors in-patients who had open or laparoscopic operation between April1990and December2007in our hospital is taken as research object, collected its paraffin embedded tissues samples after operation, and combined with pathology report and clinical data to confirm that there are45cases adrenocortical adenoma,14cases adrenocortical carcinoma,26cases pheochromocytoma and6cases malignant pheochromocytoma in the91cases patients. The21cases normal adrenal glands were all from corpus renal for kidney transplantation. The normal adrenal and PBS were selected as positive control and negative control, and we detected the expression level of Cx26、Cx32and Cx43in112cases, a slice was selected for HE dye in each group and all of normal adrenal were dyed for rejecting other pathologic changes. Fourteen cases of adrenocortical carcinoma and five cases of malignant pheochromocytoma patients had Complete follow-up data. We used statistical methods to deal with the expressions of Cx26、 Cx32and Cx43, and analyse the relation between the age, sex, clinical stage of tumors, prognosis and Cx26、Cx32and Cx43, and analyse the correlation between the three different gap junction protein as well.[Results]1、The positive intensity of expression Cx26,Cx32and Cx43in the normal adrenal gland,adrenal cortical adenoma,adrenal cortical carcinoma are significantly difference(χ2=21.366,P=0.000;χ2=17.509,P=0.000;χ2=22.645,P=0.000).The positive intensity expression of Cx26,Cx32and Cx43in adrenal cortical carcinoma followed by less than adrenocortical adenoma and normal adrenal.The positive intensity of expression of Cx26in normal adrenal gland,pheochromocytoma and malignant pheochromacytoma are significantly difference(χ2=43.717,P=0.000), the highest in malignant pheochromocytoma and the lowest in pheochromocytoma.There were negative expression of Cx32and Cx43in pheochromaocytoma and malignant pheochromacytoma.2、Cx32, Cx43expression in adrenal cortical carcinoma was positively correlated (r=0.646, respectively, P=0.013);Cx26、Cx32in adrenal cortical carcinoma expression had no correlation (r=0.356, P=0.212); Cx26、Cx43in the gland cortex carcinomaexpression showed no correlation (r=0.392,P=0.165).Log-Rank Univariate analysis showed that age,clinical stage,positive expression of Cx43is the influencing factors of the cortical cancer survival time. 3、The expression of Cx43was closely related to the prognosis of adrenal cortical carcinoma (B=-1.962, P=0.030),the lower expression of Cx43, the worse prognosis of patients.[Conclusion]1、Joint detecting Cx26、Cx32and Cx43in adrenal cortical tumors has important reference value on differentiating benign adrenal cortical tumors from malignant adrenal cortical tumors.2、The detection of Cx26in adrenal medullary tumors has important significance in differentiating malignant pheochromocytoma and pheochromocytoma.3、The expression of Cx43in primary adrenal cortical carcinoma tissues is related to the prognosis of patients, increasing its expression may improve the prognosis of patients. |
PDF Full Text Request