Expression And Significance Of MAGE-A Family Members And NY-ESO-1 In Breast Cancer Tissues

In China, the incidence of breast cancer accounted for the first in women malignant tumor. In recent years, the development of tumor associated antigen has become one of the focuses in the field of tumor immunotherapy. Among the numerous known tumor-associated antigens, the cancer/testis antigens(CTA) displayed the specific expression pattern. CTA was a suitable target antigen for specific tumor immunotherapy. This article takes melanoma antigen gene(MAGE) which is a sub-family of CTA as the research object.As a sub-family of CTA, NY-ESO-1 has strong immunogenicity and are expressed in multiple malignant tumors(malignant melanoma, liver cancer, ovarian cancer, etc). NY-ESO-1has got great attention.In our study, immunohistochemistry was used to detect MAGE-A family members(including MAGE-A1,-A2,-A3,-A4,-A6,-A10 and-A12, called MAGE-As) and NY-ESO-1 protein expressions in normal breast tissues and breast cancer tissues, and the correlation between their expressions and the clinic pathological features of breast cancer was analyzed. The conclusion could provide a theoretical basis for MAGE-As and NY-ESO-1 to become a target of breast cancer biological therapy.To investigate expressions of MAGE-As(includingObjective: To investigate expressions of MAGE-As(including MAGE-A1,-A2,-A3,-A4,-A6,-A10 and-A12) and NY-ESO-1 proteins in breast cancer tissues and normal tissues, and analyze the relationship between their expression and the clinic pathological features.Methods: Immunohistochemical staining was adopted to detect expressions of MAGE-As and NY-ESO-1 proteins in breast cancer tissues and normal breast tissues, and the relationship between their expression and the clinic pathological features was retrospectively analyzed.Results: 1 There was no MAGE-As protein expression in 61 normal breast tissues. MAGE-As protein expression was detected in 38 of 61 breast cancer tissues(63.3%), suggesting that MAGE-As was tumor-specific antigen. 2 Relationship between MAGE-As expression and the clinic pathological features of breast cancer Immunohistochemical staining results showed that the part of MAGE-As was located in cytoplasm and another part of MAGE-As was located in cell nucleus. MAGE-As protein expression was detected in 11 of 35 HER-2(-~++) breast cancer patients and in 16 of 26 C-erb B2(+++) breast cancer patients, and the positive rates were 75% and 50%, with significant difference(χ~2=5.482, P=0.019). There were no significant differences between MAGEAs protein expression and other clinic pathological features of breast cancer including age of the patients(χ~2=0.691, P=0.406), histological grade(χ~2=3.773, P=0.152), clinical stages((χ~2=2.469, P=0.291), tumor size(χ~2=4.156, P=0.125), metastasis of axillary lymph nodes(χ~2=0.021, P=0.886), P53 status(χ~2=0.240, P=0.624), PR status(χ~2=2.861, P=0.091) and VEGF(χ~2=0.322, P=0.570)(P>0.05). 3 Expression of NY-ESO-1 protein in normal breast tissues and breast cancer tissues. Immunohistochemical staining results showed that the part of NY-ESO-1 was located in cytoplasm and another part of NY-ESO-1 was located in cell nucleus. Expression NY-ESO-1 protein was detected in 6 of 61 normal breast tissues and 23 of 61 breast cancer tissues, and the positive rate was 9.83% and 37.7%, respectively, with significant difference(χ~2=13.073, P=0.000). 4 Relationship between NY-ESO-1 expression and the clinic pathological features of breast cancer Expression of NY-ESO-1 protein was detected in 4 of 22 ER negative breast cancer patients and in 19 of 39 ER positive breast cancer patients, and the positive rates were 18.2% and 48.7%, with significant difference(χ~2=5.584, P=0.018). There were no significant differences between NY-ESO-1 protein expression and other clinic pathological features of breast cancer including age of the patients(χ~2=0.087, P=0.768), histological grade(χ~2=5.740, P=0.057), clinical stages(χ~2=1.520, P=0.468), tumor size(χ~2=1.193, P=0.551), metastasis of axillary lymph nodes(χ~2=3.062, P=0.080) and HER-2 status(χ~2=1.377, P=0.241), P53 status(χ~2=1.699, P=0.192), PR status(χ~2=0.032, P=0.858)(P>0.05). 5 Relationship between MAGE-As expression and NY-ESO-1 expression in breast cancer 28 of 61(45.9%) breast cancer tissues showed MAGE-As or NY-ESO-1 expression. 11 of 61(18.03%) breast cancer tissues showed MAGE-As and NY-ESO-1 expression. There is no correlation between MAGE-As and NY-ESO-1 expressions.(r=0.056, P>0.05).Conclusions: MAGE-As(Including MAGE-A1,-A2,-A3,-A4,-A6,-A10 and-A12), and NY-ESO-1 proteins are tumor-associated antigens with high specificity in breast cancer. There was a positive correlation between MAGE-As protein expression and HER-2 protein expression, which is a poor prognostic marker for breast cancer. MAGE-As and NY-ESO-1 expressions are positively related to ER. Both MAGE-As and NY-ESO-1 could be used as immunotherapeutic targets for breast cancer.