HDAC6 mRNA expression is correlated with better prognosis in breast cancer
aNagoya City University Graduate School of Medical Sciences, Nagoya, Japan, bDivision of Endocrinology, Saitama Cancer Center Research Institute, Saitama, Japan
AIM: Gene expression patterns using microarray in MCF-7 cells showed that histone actylase 6 (HDAC6) gene was one of the early-responsive estrogen-induced genes (J Molecular Endocrinology, 29, 2002). This led us to hypothesize that there was a link between levels of HDAC6 expression and the hormone dependent potential of breast cancer. METHOD: In the present study, the level of HDAC6 mRNA expression was analyzed using quantitative real-time RT-PCR in158 patients with invasive breast cancer and the protein expressions were also determined by immunohistochemistry. RESULTS: HDAC6 mRNA was expressed at significantly higher levels in breast cancer patients with small tumors measuring less than 2 cm, with non-high histological grade of the tumor, and in estrogen receptor (ER) a and progesterone receptor (PgR) positive tumors. Patients expressing high levels of HDAC6 mRNA have a statistically better prognosis than those expressing low levels. Furthermore, the patients with high levels of HDAC6 mRNA tended to be more responsible to endocrine treatment than those with low levels. Specific staining was found in the nucleus of some normal epithelial cells and in the cytoplasm of the majority of cancer cells. However, no relationship was found between HDAC6 cytoplasmic expression and any clinicopathologic factors or survival. CONCLUSION: We conclude that the expression levels of HDAC6 mRNA could have potential both as a prognostic marker and as a predictive marker for endocrine treatment in breast cancer.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 892 (Susceptibility genes).