Kouroukli Olga, Bravou Vasiliki, Giannitsas Konstantinos, Tzelepi Vasiliki
Department of Pathology, Evaggelismos General Hospital, 10676 Athens, Greece.
Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, 26504 Patras, Greece.
Cancers (Basel). 2024 Feb 16;16(4):805. doi: 10.3390/cancers16040805.
Prostate cancer (PC) is a common malignancy among elderly men, characterized by great heterogeneity in its clinical course, ranging from an indolent to a highly aggressive disease. The aggressive variant of prostate cancer (AVPC) clinically shows an atypical pattern of disease progression, similar to that of small cell PC (SCPC), and also shares the chemo-responsiveness of SCPC. The term AVPC does not describe a specific histologic subtype of PC but rather the group of tumors that, irrespective of morphology, show an aggressive clinical course, dictated by androgen receptor (AR) indifference. AR indifference represents an adaptive response to androgen deprivation therapy (ADT), driven by epithelial plasticity, an inherent ability of tumor cells to adapt to their environment by changing their phenotypic characteristics in a bi-directional way. The molecular profile of AVPC entails combined alterations in the tumor suppressor genes retinoblastoma protein 1 (RB1), tumor protein 53 (TP53), and phosphatase and tensin homolog (PTEN). The understanding of the biologic heterogeneity of castration-resistant PC (CRPC) and the need to identify the subset of patients that would potentially benefit from specific therapies necessitate the development of prognostic and predictive biomarkers. This review aims to discuss the possible pathophysiologic mechanisms of AVPC development and the potential use of emerging tissue-based biomarkers in clinical practice.
前列腺癌（PC）是老年男性中常见的恶性肿瘤，其临床病程具有高度异质性，从惰性疾病到高度侵袭性疾病不等。前列腺癌的侵袭性变体（AVPC）在临床上表现出非典型的疾病进展模式，类似于小细胞前列腺癌（SCPC），并且也具有与SCPC相同的化疗反应性。AVPC这一术语并非描述PC的特定组织学亚型，而是指一组肿瘤，无论其形态如何，均表现出由雄激素受体（AR）不敏感性所决定的侵袭性临床病程。AR不敏感性代表了对雄激素剥夺治疗（ADT）的一种适应性反应，由上皮可塑性驱动，上皮可塑性是肿瘤细胞通过双向改变其表型特征来适应环境的一种固有能力。AVPC的分子特征包括肿瘤抑制基因视网膜母细胞瘤蛋白1（RB1）、肿瘤蛋白53（TP53）和磷酸酶及张力蛋白同源物（PTEN）的联合改变。对去势抵抗性前列腺癌（CRPC）生物学异质性的理解以及识别可能从特定治疗中获益的患者亚组的需求，促使人们开发预后和预测生物标志物。本综述旨在讨论AVPC发生的可能病理生理机制以及新兴的基于组织的生物标志物在临床实践中的潜在应用。
