Revealing neuroendocrine transformation in gynecological cancers through genomic analysis

Neuroendocrine transformation (NT) in cancers, typically observed under the selective pressure of targeted therapies, involves lineage plasticity where adenocarcinomas adopt neuroendocrine characteristics while retaining the molecular alterations of their original histology. This phenomenon, well-documented in prostate and lung cancers, has not been observed in gynecological malignancies until now. We present two pivotal cases involving primary ovarian and uterine cancers that developed neuroendocrine carcinomas post-treatment. Initially presumed to be independent primaries, comprehensive next-generation sequencing technologies, including UW-OncoPlex and BROCA panels, were used to establish a clonal relationship between the primary tumors and their respective neuroendocrine metastases. This report provides the first documented instances of NT in gynecological cancers, indicating that it may be a more widespread resistance mechanism than previously recognized. Routine re-biopsy and early integration of advanced molecular diagnostics into clinical practice will identify NT and provide insights into pathogenesis and eventual therapeutic options.