biostudies-literature00450Unknown48(12)Ruschoff JHUniversität Zürich<h4>Purpose</h4>Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding ⁶⁸Ga-PSMA-11-PET examinations.<h4>Methods</h4>RPE specimens of 62 patients with preoperative ⁶⁸Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA_%neg) were correlated with spatially corresponding SUV_max on ⁶⁸Ga-PSMA-11-PET in a multidisciplinary analysis.<h4>Results</h4>All tumours showed medium to strong membranous (2-3 +) and weak to strong cytoplasmic (1-3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA_%neg. PSMA_%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUV_max values. A ROC curve analysis revealed 20% PSMA_%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA_%neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan.<h4>Conclusions</h4>We describe PSMA_%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower ⁶⁸Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.European journal of nuclear medicine and molecular imaging4042-4053https://www.ebi.ac.uk/biostudies/studies/S-EPMC8484204biostudies-literatureWhat's behind ⁶⁸Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns.PMC8484204Moch HHermanns TRuschoff JHBurger IARupp NJMuehlematter UJRodewald AKEberli DFerraro DALaudicella R45falseWhat's behind ⁶⁸Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns.<h4>Purpose</h4>Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding ⁶⁸Ga-PSMA-11-PET examinations.<h4>Methods</h4>RPE specimens of 62 patients with preoperative ⁶⁸Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA_%neg) were correlated with spatially corresponding SUV_max on ⁶⁸Ga-PSMA-11-PET in a multidisciplinary analysis.<h4>Results</h4>All tumours showed medium to strong membranous (2-3 +) and weak to strong cytoplasmic (1-3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA_%neg. PSMA_%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUV_max values. A ROC curve analysis revealed 20% PSMA_%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA_%neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan.<h4>Conclusions</h4>We describe PSMA_%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower ⁶⁸Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.2021-01-01T00:00:00Z2021 Nov2024-02-15T11:13:45.778Z2022-02-11T11:43:26.686ZS-EPMC84842043438683910.1007/s00259-021-05501-1