Immunohistochemical validation of PSMA expression measured by 68 Ga-PSMA PET/CT in primary prostate cancer

Abstract

68 Ga-labeled prostate-specific membrane antigen ( 68 Ga-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 68 Ga-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 5 31), median staining intensity was mild, median percentage of stained cells was 20% 6 14.24%, and median immunoreactive score (IRS) was 1. In PCA sections (n 5 31), median IRS was 3, median staining intensity was strong, and median percentage of stained cells was 80% 6 16.46%. The mean SUV max (6SD) of PCA (14.06 6 15.56) was significantly higher than that of PN (2.43 6 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 5 26; 2.52 6 0.64) was significantly lower than the mean SUV max for an IRS of 2 or more (n 5 36; 12.38 6 15.02; P, 0.001). The mean SUV max was significantly lower in PCA samples with fewer than 50% stained cells (n 5 30; 2.81 6 2.35) than in samples with 50% or more (n 5 32; 13.34 6 15.55; P, 0.001). There was no correlation between the SUV max of PCA and Gleason score (P 5 0.54). Conclusion: This study showed that SUV max on 68 Ga-PSMA PET/CT correlates significantly with PSMA expression in primary PCA, enabling the detection of PCA with a high sensitivity and specificity.