Immunohistochemical Validation of PSMA Expression Measured by 68Ga-PSMA PET/CT in Primary Prostate Cancer

Abstract

⁶⁸Ga-labeled prostate-specific membrane antigen (⁶⁸Ga-PSMA) PET/CT has a proven role in staging and restaging of prostate cancer (PCA). The aims of this study were to evaluate the association of intraprostatic ⁶⁸Ga-PSMA PET/CT findings and PSMA expression in immunohistochemical staining and generate a cutoff value for differentiation between normal prostate (PN) and PCA. Methods: The data of 31 patients (mean age, 67.2 y) who underwent prostatectomy and preoperative PET were retrospectively analyzed. On PET, focally increased uptake in the prostate was suggestive of tumor. A region of interest was placed on the suggestive area to generate an SUV_max; a similar region of interest was placed on adjacent visually PN. Both PCA and PN were stained with monoclonal anti-PSMA antibody (clone 3E6, 1:100, M3620). Results: All intraprostatic PCA lesions on PET could be confirmed histopathologically. In PN sections (n = 31), median staining intensity was mild, median percentage of stained cells was 20% ± 14.24%, and median immunoreactive score (IRS) was 1. In PCA sections (n = 31), median IRS was 3, median staining intensity was strong, and median percentage of stained cells was 80% ± 16.46%. The mean SUV_max (±SD) of PCA (14.06 ± 15.56) was significantly higher than that of PN (2.43 ± 0.63; P < 0.001). Receiver-operating-characteristic curve analyses of the SUV_max of PCA, validated by immunohistochemical staining in 62 tissue samples, showed the best cutoff to be 3.15 (sensitivity, 97%; specificity, 90%; area under curve, 0.987). Applied to multifocal PCA, it resulted in sensitivity and specificity of 87% and 97% respectively. The mean SUV_max of PCA and PN for an IRS of less than 2 (n = 26; 2.52 ± 0.64) was significantly lower than the mean SUV_max for an IRS of 2 or more (n = 36; 12.38 ± 15.02; P < 0.001). The mean SUV_max was significantly lower in PCA samples with fewer than 50% stained cells (n = 30; 2.81 ± 2.35) than in samples with 50% or more (n = 32; 13.34 ± 15.55; P < 0.001). There was no correlation between the SUV_max of PCA and Gleason score (P = 0.54). Conclusion: This study showed that SUV_max on ⁶⁸Ga-PSMA PET/CT correlates significantly with PSMA expression in primary PCA, enabling the detection of PCA with a high sensitivity and specificity.

Keywords: 68Ga-PSMA PET/CT; SUVmax cutoff; immunohistochemistry; prostate cancer; prostate specific membrane antigen.