AUTHOR=Droghetti Matteo , Bianchi Lorenzo , Presutti Massimiliano , Vetrone Luigia , Farolfi Andrea , Mei Riccardo , Giunchi Francesca , Degiovanni Alessio , Mottaran Angelo , Piazza Pietro , Cangemi Danilo , Castellucci Paolo , D’Errico Antonietta , Schiavina Riccardo , Brunocilla Eugenio , Fanti Stefano 

TITLE=Immunohistochemistry analysis of PSMA expression at prostatic biopsy in high-risk prostate cancer: potential implications for PSMA-PET patient selection

JOURNAL=Frontiers in Oncology

VOLUME=Volume 14 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1324631

DOI=10.3389/fonc.2024.1324631

ISSN=2234-943X

ABSTRACT=Prostate-specific membrane antigen (PSMA) is a trans-membrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) have grown particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET result and many tools have been proposed to improve patients' selection.Furthermore, PSMA expression is not homogeneous among different tissues, and within the prostate itself. The aim of this study was to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole mount specimen and with PSMA-PET parameters.We included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our Institution from January 2022 to December 2022. PET parameters selected were SUVmax, total volume (TV) and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score(VS) (1, 2, 3) visual pattern(VP) (membranous, cytoplasmatic and combined) and percentage of PSMA-negative tumour areas (PSMA%neg) within biopsy cores were evaluated.43 patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen's kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg<20% had higher concordance in VS and VP (Cohen's kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p=0.3) and PSMA-TL (p=0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p=0.04). Higher SUVmax was associated with membranous and combined VP expression (p=0.008). No difference emerged between patients with PSMA%neg<20% or PSMA%neg>20% at biopsy cores in terms of SUVmax, PSMA-TL and PSMA-TV (p=0.5, p=0.5, p=0.9 respectively).We found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score.