| Background and objectiveCervical cancer is early detected timely and treated effectively through widely screening cervical cancer. But cervical cancer is still the most common gynecological malignant tumor in China and a serious threat to the lives and health of women. Although cervical cancer surgery and radiation therapy have become increasingly mature, curative effect is unsatisfactory for locally advanced cervical cancer and recurrent metastasis of cervical cancer. Chemotherapy as one method of cervical cancer treatments, is paid more and more attention. However, the therapeutic effect is more limited, often with chemotherapy drug resistance. Biological molecular target therapy is a new generation of anti-tumor therapy following cytotoxic chemotherapy drugs, and it has been proved to be possible and effective by some clinical trials in cervical cancer. But there are still a lot of problems unsolved, such as the heterogeneity of antibody, drug resistance caused by compensatory gene mutation and tumor signaling, adverse reactions and toxic effects, and the treatment of economic consideration. Therefore, the new target molecule of biological therapy needs to be found for improving the treatment effect of cervical cancer,δ receptor is non-opioid receptor and one type of independent receptors with highly conservative mammalian proteins. It is expressed in various tissues, suggesting that it plays an important role in cellular function. Two subtypes have been identified, termed al receptor and δ2receptor. The gene and protein structure of al receptor are generally clear, but of δ2receptor are not clear yet. The relative molecular mass of δ2is19-21.5kDa. The latest research shows that δ2is most likely the receptor composition1of progesterone receptor membrane (PGRMC1). In the past, most of the researches of al receptor ligands were focused on mental disorders. The researches in recent years found that al receptor is closely related to tumor, al receptor ligands are used in the diagnosis of malignant tumors in some prospective researches as a target for anti-tumor treatment, which suggests the potential application value of al receptor when dealing with malignant tumors. Some preliminary studies show that al receptor can be highly expressed in many tumor cells including cervical cancer cells. At present, we haven’t seen any literature about al receptor expressed in cervical cancer tissue both at home and abroad. The discovery of this study is al receptor expression in cellular nucleus, which is associated with the pathological type of cervical cancer and prognosis.Materials and Methods160cases of paraffin embedded blocks of cervical tissue were obtained from January2007to December2012at Department of Pathology, the Second Affiliated Hospital of Zhengzhou University, including30cases of normal cervix,42cases of cervical intraepithelial neoplasia, and88cases of cervical cancer, including70cases of cervical squamous carcinoma,18cases of cervical adenocarcinoma.88case of cervical cancer have complete clinical material. All cervical tissue blocks were pathologically confirmed. SP immunochistochemistry technique was used to detect the expression of al receptor. Fluorescence immunochemical experiment was conducted to further validate the expression location of al receptor, al receptor antibodies were purchased from Santa Cruz and Sigma-Aldrich of USA. All patients of cervical cancer were follow-uped and recorded. Their survival time was documented, and the cut-off time of follow-up time was December20,2012.The criteria of al receptor expression:immunostaining result was scored, based on for the relative immunostaining intensity and appropriate percentage of positive tumor cell. It was defined as the mark of positive cell that cervical epithelial cell cytoplasm and or nuclei appear pale yellow to yellow-brown. According to the percentage of positive cells and the color depth, al receptor expression was divided four grades:no staining, weak, intermediate, and strong immunoreactivity. al receptor expression in cellular nucleus was found in this experiment. For nuclei positive cases, immunostaining results were also scored according to the relative immunostaining intensity and appropriate percentage of positive tumor cells. The cases of equal to or more than3scores were defined as positive expression of al receptor.The date were analyzed by SPSS17.0statistical software. Rank sum test was used for comparison of the different levels of data, X2testing for the qualitative data. Survival rates were calculated by the Kaplan-Meier method, and differences were examined by the Log-rank. Inspection level is α=0.05. For the comparison in each team, inspection level is α’=0.05/k, k as comparison times.Result1. Expression location of al receptor in the tissues of normal cervix, cervical intraepithelial neoplasia and cervical cancer:cytoplasmic al receptor expression existed in the three kinds of cervical tissues. The phenomenon of nuclear al receptor expression in the tissue of cervical cancer was confirmed and identified by SP immunochistochemistry technique and fluorescence immunochemical experiment.2. The comparison of al receptor expression among the tissues of normal cervix, cervical intraepithelial neoplasia and cervical squamous carcinoma:the expression of al receptor existed in the three groups, al receptor staining intensity and positive cell rate increased gradually with the increase in the degree of cervical lesions. Rank sum test showed that the expression difference was statistically significant among three kinds of cervical tissues,.P=0.000; the expression of al receptor in normal cervix was significantly lower than that in cervical squamous carcinoma and cervical intraepithelial neoplasia, P=0.015and0.000respectively; al receptor expression in cervical squamous carcinoma was significantly higher than that in cervical intraepithelial neoplasia, P=0.002.3. The relationship between expression of al receptor and clinicopathological parameters of cervical cancer:in the tissue of cervical squamous carcinoma, δ1receptor expression is not associated with patient age, the tissue differentiation, and clinical stage; the expression of al receptor is significantly associated with pathological type, the expression of δ1receptor in cervical adenocarcinoma was significantly higher than that in cervical squamous carcinoma, P=0.030.4. The comparison of al receptor expression in cellular nucleus between cervical adenocarcinoma and cervical squamous carcinoma:al receptor expression in cellular nucleus does not exist in normal cervix and cervical intraepithelial neoplasia. δ1receptor expression in cellular nucleus is widespread existing, especially in cervical adenocarcinoma. The nucleus expression rate is55.56%in cervical adenocarcinoma, and27.14%in cervical squamous carcinoma. There was the significant difference in between two groups, P=0.024.5. The relationship between al receptor expression in the tissue of cervical carcinoma and survival time of cervical carcinoma:in the tissue of cervical squamous carcinoma, the median overall survival (MOS, month,45.508±2.958) of δ1receptor positive-expression cases was significantly lower than the MOS(55.759±6.955) of al receptor negative-expression cases, P=0.048; The MOS(41.008±3.541) of al receptor nucleus-expression cases was significantly lower than the MOS(47.442±2.850) of δ1receptor cytoplasmic-expression cases, P=0.003; The MOS(35.000±6.345) of al receptor nucleus-expression cases in cervical adenocarcinoma was significantly lower than the MOS(44.186±4.253) of δ1receptor nucleus-expression expression cases in cervical squamous carcinoma, P=0.034.Conclusions1. δ1receptor is overexpressed in cervical cancer and cervical intraepithelial neoplasia.2. δ1receptor expression in cellular nucleus exists in cervical cancer tissue, which is an important mark of cervical adenocarcinoma.3. δ1receptor expression, especially nucleus expression, may be associated with poor prognosis. |
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