Retrospective clinical and molecular characterisation of patients with penile intraepithelial neoplasia

To provide the first comprehensive molecular characterisation of penile intraepithelial neoplasia (PeIN) and to define the molecular alterations and clinical parameters associated with recurrence in order to enhance our ability to manage this disease.

We conducted a retrospective audit of records and an analysis of archived formalin-fixed paraffin-embedded (FFPE) tissue from a single-centre population-based consecutive sample, to characterise the genetic landscape of 28 PeIN patients through DNA copy number analysis, RNA expression analysis, and gene set enrichment analysis (GSEA). The primary and secondary study outcomes were alterations in the genetic landscape of recurring vs non-recurring PeIN and clinical risk factors for recurrence.

In patients with PeIN recurrence, we identified seven significantly overexpressed genes (e.g., MYC, SCN8A and PSTK). Importantly, in the DNA analysis, the MYC locus was amplified (8q24.12-8q24.22 gain), the RNA analysis showed overexpression of MYC, and the MYC pathways (GSEA) were enriched compared to patients without PeIN recurrence. Limitations of the study include treatment heterogeneity and FFPE specimens challenging for RNA quality.

We identified seven overexpressed genes in patients with PeIN recurrence. Some of these transcripts were previously reported to be involved in invasive penile cancer. These findings provide molecular evidence, that PeIN is a precursor lesion with a correlation to invasive penile cancer, and could potentially lead to new topical treatment strategies for PeIN and low-risk penile cancer.