Heterogeneous Expression Of Two Cancer/Testis Antigens: Correlatione With The Prognosis Of The Human Breast Carcinoma

Cancer/testis antigens (CTAs) are a group of tumor-associated antigenswith restricted expression in normal adult testicular germ cells and aberrantexpression in a variety of human tumors. CTAs are the promising tumourmarkers as their expression closely correlated with the occurrence anddevelopment of tumour. At present,138CTAs gene families encoding a totalof204transcripts have been found. However, the lag of the research on CTAat protein level greatly restricted their application in tumor diagnosis andtreatment.In this study, BALB/c mice were immunized with recombinant CT47protein and the spleen cells from the immunized mice were fused withmyeloma cells of SP2/0. After screening and cloning, a total of16hybridomacell lines (designated FMU-CT47-1～FMU-CT47-16) secretingCT47-specific monoclonal antibodies were obtained. Indirect ELISA was performed to detect the Ig subclasses and titers of the ascites. Monoclonalantibody FMU-CT47-5was selected for the immunohistochemistryexperiment.The identification of the specificity of CT47mAb was carried outby the testicular tissue microarray. With the selected monoclonal antibodies,the expression of CT47protein was detected in normal tissues and tissuesample from300cases of breast carcinoma. The results showed that inaddition to expression in the cytoplasm of the spermatogonia of the normaltesticular tissue, CT47protein also expressed in the cytoplasm of normalpancreatic ductal epithelial cells and bladder transitional cells. CT47proteinwas not expressed in normal breast tissue, but expression in breast cancertissues and with the frequency of36.0%. Moreover, the expression of CT47protein in breast cancer associated with the differentiation, progression andprognosis of breast cancer suggesting the CT47protein may be used as adiagnostic marker of breast cancer.Using CT10-specific monoclonal antibodies and the method ofimmunohistochemistry,the expression of CT10protein was studied in thetissues of420cases of patients with breast invasive ductal carcinoma. Theresults showed that the frequency of CT10protein expression in breast cancertissues was27.1%. The CT10protein expressed in the nuclei of breast cancercells. According to the different distribution of positive cells, the expressionpattern of CT10protein can be divided into punctate, focal and diffusesexpression patterns. Using the method of immunohistochemical scoring, thequantity of CT10protein expression in breast carcinoma was evaluated.Patients with CT10positive expression were divided into two groups of high CT10expression and low CT10expression. The results showed that the breastcarcinoma patients with CT10highly expressed were associated with thelymph node grading, distant metastasis, clinical stage and NottinghamPrognostic Index of breast carcinoma. Analysis of disease-free survival andoverall survival of the two groups of patients, indicated that the disease-freesurvival and overall survival of patients with CT10high expression wereshorter than that of patients with CT10low expression suggesting that CT10protein may promote the development of breast cacinoma and has a negativecorrelation with prognosis of breast cacinoma.In summary, we systematically analyzed the expression pattern of CT47and CT10, and further analyzed the correlation of these two CTAs expressionwith the prognosis of breast cacinoma.which may provide an important basisfor CT47and CT10in diagnositic and prognostic markers of breastcarcinoma.