Immune molecular profiling of a multiresistant primary prostate cancer with a neuroendocrine-like phenotype: a case repo
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CASE REPORT
Immune molecular profiling of a multiresistant primary prostate cancer with a neuroendocrine‑like phenotype: a case report Scott G. Williams1,2,4, Han Xian Aw Yeang3,5, Catherine Mitchell4, Franco Caramia2, David J. Byrne4, Stephen B. Fox4, Sue Haupt2,5, Ralf B. Schittenhelm6,7, Paul J. Neeson3,5, Ygal Haupt2,5,7† and Simon P. Keam2,3,5*†
Abstract Background: Understanding the drivers of recurrence in aggressive prostate cancer requires detailed molecular and genomic understanding in order to aid therapeutic interventions.We provide here a case report of histological, transcriptional, proteomic, immunological, and genomic features in a longitudinal study of multiple biopsies from diagnosis, through treatment, and subsequent recurrence. Case presentation: Here we present a case study of a male in 70 s with high-grade clinically-localised acinar adenocarcinoma treated with definitive hormone therapy and radiotherapy. The patient progressed rapidly with rising PSA and succumbed without metastasis 52 months after diagnosis.We identified the expression of canonical histological markers of neuroendocrine PC (NEPC) including synaptophysin, neuron-specific enolase and thyroid transcription factor 1, as well as intact AR expression, in the recurrent disease only.The resistant disease was also marked by an extremely low immune infiltrate, extensive genomic chromosomal aberrations, and overactivity in molecular hallmarks of NEPC disease including Aurora kinase and E2F, as well as novel alterations in the cMYB pathway. We also observed that responses to both primary treatments (high dose-rate brachytherapy and androgen deprivation therapies) were consistent with known optimal responses—ruling out treatment inefficacy as a factor in relapse. Conclusions: These data provide novel insights into a case of locally recurrent aggressive prostate cancer harbouring NEPC pathology, in the absence of detected metastasis. Keywords: Case report, Neuroendocrine, Localized, Brachytherapy, Hormone therapy Background Prostate cancer (PC) that recurs after primary treatment is a significant health issue. While the initial response rate to conventional therapy is high, most recurrences *Correspondence: [email protected] † Ygal Haupt and Simon P. Keam: shared senior author. 2 Tumor Suppression Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia Full list of author information is available at the end of the article
will progress to become resistant to ongoing salvage therapies, with high rates of lethal progression. More unusually, there are a subset of cancers that are refractory to therapies such as androgen deprivation therapy (ADT) de novo and carry a worse prognosis via rapid progression [1]. Identifying the molecular progression and the genomic features of these tumours will aid in early identification, treatment selection and novel therapeutic development.
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits
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