Introduction:

PSMA is expressed in the renal proximal tubule and by endothelial cells within the blood vessels of some tumors, including renal cell cancer (RCC). This study evaluated PSMA expression heterogeneity and prognostic association of PSMA expression in localized RCC using automated quantitative immunohistochemistry.

Methods:

Tissue microarrays (TMAs) were created from non-metastatic clear cell RCC (ccRCC) patients, sampling 8 regions of each tumor and 3 samples from adjacent benign kidney tissue to determine PSMA expression. Two cohorts were evaluated: patients who progressed to metastatic disease and those who did not. Cohorts (progressed vs not progressed) were matched on age, gender, performance status, pT-stage, grade, and tumor size. PSMA expression was analyzed for associations with vascular endothelial cell density (CD31⁺ cells/mm²) and a previously published tumor-associated neovascularity index (CD105⁺/CD31⁺ ratio). Kernel density plots were used to demonstrate tissue heterogeneity.

Results:

A total of 506 tissue samples were used to construct TMAs from 46 matched ccRCC patients in 2 cohorts: 26 patients developed metastatic progression with a median follow-up of 7 years (IQR 5-11), while 20 patients had no progression with a median follow-up of 11 years (IQR 8-15). Overall, the median tumor size was 9 cm.

PSMA expression was highly heterogeneous throughout RCC tumors (Fig 1A, B). PSMA expression was higher in benign renal tissue than RCC and among tumors that did not progress (Fig 1C). PSMA was positively correlated with normal endothelial cell density (Spearman r = 0.32; P = 0.001) and negatively correlated with neovascularity (r = -0.29; P < 0.001). After multivariable analysis, higher PSMA expression was associated with improved progression-free survival (HR 0.46, P < 0.001) (Fig 1D).

Conclusion:

PSMA expression demonstrates heterogeneity across tumor samples, in part reflecting endothelial cells and vascularity. PSMA was inversely correlated with tumor-associated neovascularity. 

In non-metastatic ccRCC, average tumor PSMA expression may be a positive prognostic marker for RCC, warranting further clinical investigation.

Funding: N/A