The Expression And Significance Of Human Endogenous Retrovirus Envelope (HERV-K Env) Gene In Human Breast Cancer

Objective:To assess the expression of Human endogenous retrovirus K envelop (HERV-K env) gene in different breast tissues and to analyze the association of its expression with clinicopathologic characteristics and prognosis of breast cancer patients.Methods:1. Semi-quantitative reverse transcription polymerase chain reaction was used to detect the expression of HERV-K env in 40 cases of breast cancer,40 cases of adjacent uninvolved breast tissues derived from breast carcinoma patients,40 cases of normal breast tissues derived from the patients with benign breast disease.2. Immunohistochemistry method was used to detect the expression of HERV-K env protein in 110 cases of breast cancer,30 cases of benign breast tumor tissues.Results:1. At the mRNA level, The positive expression rate of HERV-K env gene in breast cancer tissues (70%) was significantly higher than that in adjacent uninvolved breast tissues derived from breast cancer patients (20%), and so was the difference between adjacent uninvolved breast tissues (20%) and normal breast tissues derived from the patients with benign breast disease (0%). The differences of the above are both statistically significant (P<0.05). In addition, the difference of the positive expression rate of HERV-K env gene in three kinds of tissues was also statistically significant (P=0.000).2.Immunohistochemical staining results revealed that the positive expression of HERV-K env protein showed cytoplasm staining. The expression of HERV-K env protein was almost all positive, and with moderate or high level in breast cancer tissues, but low level or no expression in benign breast tumor tissues. The positive expression rate of HERV-K env protein in breast cancer (86.4%) was significantly higher than that in benign breast tumor tissues (40.0%)(P<0.05). The expression level of HERV-K env protein was correlated with some prognostic factors of breast cancer. Among the patients with breast cancer who had positive expression of HERV-K env protein, its expression level had positive correlation with the tumor size (50.0% vs 82.9%,P=0.001). clinical stage (25.0% vs 57.9% vs 80.0%, P=0.010) and the number of positive axillary nodes (51.3% vs 52.4% vs 80.0%,P=0.023), whereas, no correlation was found between its expression level and age (61.6% vs 63.6%, P=0.866), histological grade(56.9% vs 78.3%, P=0.067), or the protein expression of ER (68.2% vs 56.7%, P=0.257)/PR (63.2% vs 60.5%, P=0.796).Among the pateints with breast cancer who had positive expression of HERV-K env protein, follow-up results revealed that the expression level of HERV-K env protein was correalted with the metastasis and survival of patients (P=0.026, P=0.049). Furthermore, the Kaplan-Meier analysis showed that the survival rate of the patients with medium or low HERV-K env protein expression was higher than that in the patients with high HERV-K env protein expression, and the difference was statistically significant (P=0.047).Conclusion:1. The positive expression rate of HERV-K env mRNA was escalating gradually in normal breast tissues, adjacent uninvolved breast tissues and breast cancer tissues, this indicated that the expression of HERV-K env mRNA may be correlated with the development of breast cancer.2. The expression of HERV-K env protein was almost all positive, and with moderate or high level in breast cancer tissues, while in the majority of benign breast tumors, its expression was negative. This indicated that HERV-K env protein maybe a target for the diagnosis of breast tumor.3.The expression level of HERV-K env protein was correlated with tumor size, clinical stage, the number of positive axillary lymph node, and poor prognosis of breast cancer patients. Besides, its expression level may be correlated with the metastasis and development of breast cancer.