Potenzielle prädiktive und prognostische molekulare Marker beim fortgeschrittenen Prostatakarzinom: eine vergleichende Analyse neuroendokrin und adenokarzinomatös differenzierter Tumore

Abstract The aim of the dissertation was to conduct a clinical and molecular pathological investigation of neuroendocrine prostate carcinomas (NEPC) and compare them with conventional adenocarcinomas of the prostate. A total of 25 NEPC and 20 advanced adenocarcinomas were analyzed, all treated at the West German Tumor Center between 1998 and 2022. In addition to clinical characterization, tissue samples were examined for molecular changes, particularly the Breast Cancer Genes (BRCA)- gene mutations, using next-generation sequencing (NGS). Patient survival rates were evaluated using Kaplan-Meier analysis and Cox regression models. The results indicated that molecular pathological changes significantly influenced overall survival (OS) but had no significant impact on progression-free survival (PFS). BRCA mutations showed a trend towards shorter survival, though no significant differences in OS or PFS were found. A comparison between NEPC patients and those with adenocarcinomas revealed that NEPCs have a notably poorer prognosis. Differences were also found between primary and secondary NEPCs, both in terms of OS and PFS. The study highlights that NEPCs have a worse prognosis compared to adenocarcinomas, regardless of disease stage. Molecular changes, particularly BRCA mutations, are associated with more aggressive disease progression. Further research in larger patient cohorts is needed to validate these findings and identify potential biomarkers for NEPC diagnosis and prognosis.