The Impact of Androgen Receptor and Histone Deacetylase 1 Expression on the Prognosis of Ductal Carcinoma

Purpose: Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS.

Methods: RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases.

Results: Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] < -1 or > 1 and < 0.001). Less than ½ fold expression of , androgen receptor (), , , , , , genes was observed in the REC group compared to the no evidence of disease group. and histone deacetylase 1 () genes were selected for external validation (: log 2-FC - 1.35, < 0.001, and : log 2-FC - 0.774, < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24-20.4; = 0.023 and HR, 3.07; 95% CI, 1.04-9.04; = 0.042). High nuclear grade 3 was also associated with long-term invasive REC.

Conclusion: Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.