| Ovarian carcinoma, with the highest mortality rate among gynecological malignancies, is still difficult to diagnose and treat because of lake of early symptom, wide metastasis of cancer cells, low effect of radical surgery, easy relapse after chemotherapy. Immune diagnosis and treatment of ovarian carcinoma will be focused following gradual understand of the mechanism of tumor immune escape is gradual clear. There are some hypotheses on the mechanism by which the tumors escape from host immune surveillance. One of them is called the low expression of MHC class I molecules. It is indicated that the low expression of MHC molecules especially class I molecules causes failure of the endoantigen process, which leads to the continual growth of tumor cells . Downregulation and loss of MHC class I expression have been shown in several tumors from distinct histology. The cause of the low expression of MHC class I molecules in malignant tumor is still unknown. Transfection of MHC class I gene into tumor cells with abnormal expression of MHC class I molecules sometimes could not elevate the expression of MHC class I molecules. The results indicated that the abnormal expression of MHC class I molecules was probably not only due to the defect of MHC class transcription and translation, but also to the abnormal assembly and transportation. Several cofactors are essential for proper MHC class I molecules assembly, such as proteasome, calnexin, calreticulin, ERP57, tapasin and TAP.Tapasin is supposed to play an important role in the quality control of MHC class I molecules assembly in endoplasmic reticulum (ER). Tapasin is a 48KDa transmembrane glycoprotein. It is still unclear how tapasin controls the assembly of MHC class I molecules in ER. Several mechanisms have been proposed by which tapasin augments peptide loading, bridged the MHC class I heavy chain complex to TAP, stabilized and relented of empty MHC class I complexes in a peptide-receptive form in the ER, optimized of the peptide repertoire capable to bind to MHC class I heterodimer. Recent researches have indicated that the low expression of tapasin existed in some malignant tumor cells and it had significant correlation with HLA class I. In order to determine whether tapasin deficits were an integral part of immune escape mechanisms of ovarian epithelial carcinoma, we detected the expressions of tapasin and HLA class I in ovarian carcinoma by immunohistochemical method (SP method) and analyzed the correlation between them. It might be very useful for the further immune diagnosis and therapy of ovarian carcinoma. Materials and Methods The tissue sample from 53 women with primary ovarian epithelial carcinoma (including 24 serous carcinomas, 22 mucinous carcinomas, and 7 endometrioid carcinoma), 40 benign ovarian tumors (including 20 serous cystadenimas, 20 mucinous cystadenomas), and 30 normal ovarian tissues were collected. A SP immunohistochemistry assay was used to determine the expressions of HLA class I molecules and tapasin in those ovarian tissues, including cellular location and semi-quantitation. All the data were statistically managed with SPSS 10.0 for windows. Results1. By immunohistochemistry, positive granules of HLA class I molecules were located on the membrane. Semi-quantitative score showed that the expression of HLA class I molecules in ovarian carcinoma cells were significantly lower than that in benign ovarian tumor and normal ovarian tissues (P=0.000). In ovarian carcinoma, the expression level of HLA class I was correlation with FIGO stages: HLA class I molecules expression level in III-IV stage was significantly lower than that in I - II stage.(P=0.018).2. Tapasin was located in the cytoplasm. Expression of tapasin carcinomas in ovarian wassignificantly lower compared with those in benign tumors and normal ovarian tissues(P=0.000). 3. In ovarian carcinoma cells, low expression of tapasin was positively correlated with HLAclass I molecules (r=0.507,P=0.000). It was indicated that downregulation of HLA class... |
