Extent of immunohistochemical PSMA-expression in primary prostate cancer shows a high correlation with tumor uptake on ⁶⁸Ga-PSMA-11-PET.

Objectives: Limited data exist regarding the exact histopathological correlation between PSMA protein expression, tumor heterogeneity and functional uptake of ⁶⁸Ga-PSMA-11 on PET. Aim of this study was, to identify immunohistochemical (IHC) PSMA patterns on radical prostatectomy specimens and correlate them to corresponding ⁶⁸Ga-PSMA-PET examinations.

Methods: Retrospective, single center analysis of patients that underwent ⁶⁸Ga-PSMA-11-PET and consecutive radical prostatectomy between 2016-2018 for prostate cancer (PCa). The dominant tumor lesion was identified and stained by IHC for PSMA. Maximal tumor diameter, Gleason Score (GS), PSMA expression on a semi-quantitative 4-tiered system and percentage of expressing tumor cells (PSMA_%pos) were noted. Pathology specimens were correlated in an interdisciplinary read out with PSMA PET images and ⁶⁸Ga-PSMA-11 uptake was quantified using SUV_max in the selected tumor area. Correlation between histopathological parameters and SUV_max was assessed using Spearman correlation.

Results: 37 patients were available for this analysis. PSMA_%pos and SUV_max had a significant correlation (r=0.715, p<0.001), while IHC intensity grading did not reach significance (r=0.193, p=0.252). The mean SUV_max in lesions with PSMA_%pos ≤ 60% was 3.7 (SD 0.6, range 3.1-4.8), lesions with PSMA_%pos > 60% had a mean SUV_max of 14.9 (SD 11.5, range 3.5-48.4). All lesions (n=5) with a SUV_max below 5 and PSMA_%pos > 60% had a very heterogeneous and infiltrative growth pattern and two were smaller than 4 mm in diameter on histopathology. 25% of GS 7a lesions had PSMA_%pos ≤60%, compared to 17% GS 7b and 11% GS≥8, respectively. Limitations include retrospective design and the low number of specimens.

Conclusions: PSMA-positive tumor area showed a strong correlation with SUV_max while PSMA intensity on IHC did not reach significance. Furthermore, our data confirms a higher rate of dominantly PSMA_%pos tumors at higher GS.

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