Abstract
Primary melanoma of the genitourinary (GU) tract comprises <1% of all melanomas. Among these, male GU melanomas (MGUM) are particularly rare. Mucosal melanomas are traditionally considered to be less responsive to immune checkpoint therapy compared to cutaneous melanomas, and a recent study reported negative correlation between patient survival and PRAME (PReferentially expressed Antigen in MElanoma) expression. We explored this further using a cohort of 13 MGUMs. Most patients were white (n=12) with median age of 68y (range 51-83y); anatomic location of tumor: 5 foreskin/penile shaft, 8 urethra; 7 patients died including 4 due to progression of MGUM. Representative tumor sections were stained with (i) anti-PRAME antibody, followed by semi-quantitative analysis to determine % of positive tumor cells to the nearest decile and intensity 0/1+/2+/3+; yielding a H-score of 0-300 and (ii) anti-PD-L1 antibody (clone 28-8) to evaluate the prevalence of membranous tumor cell expression to the nearest decile, irrespective of intensity. PRAME expression was high in 12 of 13 cases (1 to 3+ in at least 70% of tumor cells; H-scores all >100, range 110-290), with the exception one tumor (1 to 3+ in 20% of tumor cells; H-score=40). There was no correlation between PRAME expression in tumor cells and (i) disease-specific survival (comparing patients that survived for 3 years but died before 4 years, versus those who lived longer, p=0.19) and (ii) tumor morphology (epithelioid vs. spindled, p=0.46). Considering 1% as cut-off for PD-L1, 11 of 13 cases showed expression in <1% of tumor cells with no obvious correlation with PRAME expression. While this pilot study is limited by the small cohort, the results suggest that PRAME expression may not correlate with patient survival. Also, the lower prevalence of PD-L1 positivity may explain the lower response to anti-PD-L1/PD1 monotherapy. However, studies using larger cohorts is essential to validate these results.
Financial Disclosure:
No current or relevant financial relationships exist.