Immunohistochemical ERG positivity is associated with decreased PSMA expression and lower visibility in corresponding [⁶⁸Ga]Ga-PSMA-11 PET scans of primary prostate cancer

TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated.

Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [⁶⁸Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA_%neg) were correlated with the corresponding SUV_max. In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated.

Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUV_max values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUV_max values. In cohort #2, findings of higher IHC-PSMA_%neg and IHC-ERG expression was confirmed with only 0-10% PSMA_%neg tumour areas in IHC-ERG-negative PCa.

IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [⁶⁸Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches.