No abstract

Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate adenocarcinoma (AdPC) cells and acts as a target for molecular imaging. However, some case reports indicate that PSMA-targeted imaging could be ineffectual for delineation of neuroendocrine (NE) prostate cancer (NEPC) lesions due to the suppression of the PSMA gene (FOLH1). These same reports suggest that targeting somatostatin receptor type 2 (SSTR2) could be an alternative diagnostic target for NEPC patients. This study evaluates the correlation between expression of FOLH1, NEPC marker genes and SSTR2. We evaluated the transcript abundance for FOLH1 and SSTR2 genes as well as NE markers across 909 tumors. A significant suppression of FOLH1 in NEPC patient samples and AdPC samples with high expression of NE marker genes was observed. We also investigated protein alterations of PSMA and SSTR2 in an NE-induced cell line derived by hormone depletion and lineage plasticity by loss of p53. PSMA is suppressed following NE induction and cellular plasticity in p53-deficient NEPC model. The PSMA-suppressed cells have more colony formation ability and resistance to enzalutamide treatment. Conversely, SSTR2 was only elevated following hormone depletion. In 18 NEPC patient-derived xenograft (PDX) models we find a significant suppression of FOLH1 and amplification of SSTR2 expression. Due to the observed FOLH1-supressed signature of NEPC, this study cautions on the reliability of using PMSA as a target for molecular imaging of NEPC. The observed elevation of SSTR2 in NEPC supports the possible ability of SSTR2-targeted imaging for follow-up imaging of low PSMA patients and monitoring for NEPC development.

Purpose: To determine the prognostic roles of breast cancer subtypes in females with operable invasive breast cancer. Experimental Design: Data of 321,958 patients from Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Breast cancer subtypes were classified into four categories according to the status of hormone receptor (HRc) and HER2: HRc(þ)/HER2(À), HRc(þ)/HER2(þ), HRc(À)/ HER2(þ), and HRc(À)/HER2(À). Results: Proportions of HRc(þ)/HER2(À), HRc(þ)/HER2(þ), HRc(À)/HER2(þ), HRc(À)/HER2(À), and unknown subtype were 70.3%, 9.4%, 3.9%, 10.4%, and 6.0%, respectively. HRc (þ)/HER2(À) showed the highest 5-year breast cancer-specific survival (BCSS) rate (95.5%), followed by HRc(þ)/HER2(þ) (94.1%), HRc(À)/HER2(þ) (89.3%), and HRc(À)/HER2(À) (83.1%). HRc(þ)/HER2(À) and HRc(þ)/HER2(þ) showed higher 5-year overall survival (OS) rates (88.4% and 88.2%, respectively) than HRc(À)/HER2(þ) and HRc(À)/HER2(À) (83.9% and 76.5%, respectively). HRc(À)/HER2(À) showed the worst BCSS irrespective of race, age, or stage. Although proportions of HRc(À)/HER2(À) in the subgroup with negative event regarding BCSS and OS were 10.4% and 10.2%, respectively, they were 34.2% and 22.7%, respectively, in the subgroup with positive event. Subtype was a significant factor in both univariable and multivariable analyses regarding both BCSS and OS (all P < 0.001). Conclusions: Breast cancer subtype was a significant independent prognostic factor regarding both BCSS and OS in multivariable analyses. HRc(þ) subtypes showed better prognosis compared with HRc(À) subtypes regarding both BCSS and OS. HRc(À)/HER2(þ) showed better prognosis than HRc(À)/HER2(À) but worse prognosis than HRc(þ) subtypes regarding both BCSS and OS. The triple-negative subtype showed the worst BCSS compared with the other subtypes irrespective of race, age, or stage.