Activity of abiraterone in rechallenging two AR-expressing salivary gland adenocarcinomas, resistant to androgen-deprivation therapy

Abstract

Androgen-deprivation therapy (ADT) has been reported to be active in androgen receptor (AR)-expressing, relapsed/metastatic (RM), salivary gland cancers (SGCs). Abiraterone, an inhibitor of androgen synthesis, has recently been approved as a second-line treatment in hormone-resistant (HR) prostate cancer (PCa) patients. Two patients with AR-positive HR-RM adenocarcinoma, NOS of the salivary glands have been treated with abiraterone. This is the first time that this agent has been reported to be active in tumors other than HRPCa. Immunohistochemical analysis showed overexpression of EGFR, HER2, and HER3 in both untreated primary tumors. Sequencing analysis revealed a TP53 non-functional mutation in one case and a PIK3CA-activating mutation in the other. In conclusion, second line activity of ADT in AR-expressing, adenocarcinoma, NOS of salivary glands further strengthens the pathogenic and therapeutic role of AR signaling in AR-positive SGCs.

Keywords: HER3; PIK3CA; TP53; abiraterone; androgen deprivation therapy; androgen receptor; salivary gland cancers.

Figure 1. Case 1: MRI performed before starting abiraterone (A); MRI done two months later, showed the evolution of the solid tumor lesion into a liquid mass (D). The DW-MRI images (B and E) demonstrated a different ADC maps, confirming the activity of the drug: the region of interest (ROI) corresponding to the tumor had a mean/standard deviation ADC value of 1200/178 in May 2012 (B) while in (E) (July 2012), the mean ADC/standard deviation value was 2410/166. Case 2: CT scan performed on March 2012 (baseline) (C) and on May 2012 (F); this latter showed a regression of the right paracardiac mass and the disappearance of a solid lesion in the lower left lobe.

Figure 2. Immunohistochemical and molecular analyses. (A) AR-positive immunostaining in tumor nuclei. (B) HER3-positive membrane and cytoplasm immunostaining. (C) Case 1: electropherogram of TP53 mutation analysis showing the missense mutation R175H in exon 5. (D) Case 2: electropherogram of PIK3CA mutation analysis showing the missense mutation H1047R in the kinase domain (exon 20).