Morphologic, Molecular and Clinical Features of Aggressive Variant Prostate Cancer

Cells

Liang Cheng¹  Antonio Lopez-Beltran²  Francesco Massari³  Gaetano Aurilio⁴  Matteo Santoni⁵  Marina Scarpelli⁶  Alessia Cimadamore⁶  Rodolfo Montironi⁶ 

[1] Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA;Department of Surgery, Cordoba University Medical School, 14071 Cordoba, Spain;Division of Oncology, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy;Medical Oncology Division of Urogenital and Head and Neck Tumours, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy;Oncology Unit, Macerata Hospital, 62012 Macerata, Italy;Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, 60126 Ancona, Italy;

关键词: prostate cancer;    aggressive variant;    anaplastic prostate cancer;    neuroendocrine prostate cancer;    aggressive variant prostate cancer;    anaplastic prostate cancer;   

DOI  :  10.3390/cells9051073

来源: DOAJ

【 摘 要 】

The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies.

【 授权许可】

Unknown