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Immunohistochemical Validation of PSMA Expression Measured by 68 Ga-PSMA PET/CT in Primary Prostate Cancer.
Journal of Nuclear Medicine 2018 Februrary
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 SUVmax ; 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 SUVmax (±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 SUVmax 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 SUVmax of PCA and PN for an IRS of less than 2 ( n = 26; 2.52 ± 0.64) was significantly lower than the mean SUVmax for an IRS of 2 or more ( n = 36; 12.38 ± 15.02; P < 0.001). The mean SUVmax 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 SUVmax of PCA and Gleason score ( P = 0.54). Conclusion: This study showed that SUVmax 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.
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