HTERT Expression In Human Breast Cancer And Non-cancerous Tissue: The Diagnodtic Effcacy And Correlation With TP53 And C-Myc Expression.

Objective Telomerase is a ribonucleoprotein complex, which is silent in normal human somatic cells but may be reactivated by a series of regulators, and cause tumorigenesis. It has been proved that telomerase reverse transcriptase (TERT) is a critical factor of telomerase activity, but the detail mechanism and the role in tumorigenesis is still not clear. This study was designed to investigate the significance of hTERT mRNA in breast carcinogenesis and to explore the diagnostic effcacy; to study the effect of tumor suppressor gene TP53 and proto-oncogene c-Myc on the expression of hTERT mRNA for offering the experimental data about hTERT as a molecular target in tumor gene therapy. Methods The expression of hTERT mRNA was examined by in situ hybridization and fluorescence quantitative real-time RT-PCR respectively in normal breast tissue nearby cancer, simple hyperplasia, atypical hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. The expression of c-Myc mRNA was examined by fluorescence quantitative real-time RT-PCR and the protein of P53 and c-myc was analyzed by immunohistochemistry. Results 1) hTERT mRNA was not detected in normal breast tissue nearby cancer and simple hyperplasia. The positive rate of hTERT mRNA in atypical hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma were 25%(5/20), 83.33%(15/18), 88%(22/25), respectively. The prevalence and intensity of hTERT mRNA expression were much greater in carcinoma than those in simple or atypical hyperplasia and normal breast tissue nearby cancer(P<0.05). The expression of hTERT was not correlated with standard prognostic factors, such as tumor size, lymph node metastasis and steroid receptor status(P>0.05). 2) The positive correlation between hTERT mRNA and P53 protein was found in breast carcinoma (γ=0.3884, P<0.05). 3) The positive rate of hTERT mRNA expression in carcinoma was 92.11%(35/38), and the N_hTERT of them was high than the cutoff (N_hTERT=10). The N_hTERT of all the benign lesions was below the cutoff. 4) The positive correlation between hTERT mRNA and c-Myc mRNA was found in breast carcinoma (γ=0.7395, P<0.01). The positive correlation was also found between hTERT mRNA and c-myc protein expression (γ=0.6118, P<0.01). Conclusion hTERT mRNA expression is closely related to themalignant transformation of breast tissue. hTERT mRNA expression is significantlyhigher in human breast carcinoma in situ than in atypical hyperplasia. Quantitativedetection of hTERT mRNA expression by fluorescence quantitative real-time RT-PCR ishelpful in differential diagnosis of these two lesions. Inactivation of TP53 and activationof c-Myc may play a role in the transcriptive activation of hTERT gene in breastcarcinoma.