Lineage plasticity and histologic transformation from prostate adenocarcinoma to neuroendocrine prostate cancer (NEPC) occurs in up to 15-20% of patients with castration-resistant prostate cancer (CRPC) as mechanism of treatment resistance and is associated with aggressive disease and poor prognosis. NEPC tumors typically display small cell carcinoma morphology with loss of androgen receptor (AR) expression and gain of neuroendocrine (NE) lineage markers. However, there is a spectrum of phenotypes that are observed during the lineage plasticity process, and the clinical significance of mixed histologies or those that co-express AR and NE markers or lack all markers is not well defined. Translational research studies investigating NEPC have used variable definitions making clinical trial design challenging. Here we discuss the diagnostic workup of metastatic biopsies to help guide the reproducible classification of phenotypic CRPC subtypes. We recommend classifying CRPC tumors based on histomorphology (adenocarcinoma, small cell carcinoma, poorly differentiated carcinoma, other morphologic variant, or mixed morphology) and immunohistochemical markers with a priority for AR, NKX3.1, INSM1, synaptophysin and cell proliferation based on Ki-67 positivity, with additional markers to be considered based on the clinical context. Ultimately, a unified workup of metastatic CRPC biopsies can improve clinical trial design and eventually practice.

中文翻译：

---

转移性去势抵抗性前列腺癌活检的病理检查框架


从前列腺腺癌到神经内分泌前列腺癌 （NEPC） 的谱系可塑性和组织学转化发生在高达 15-20% 的去势抵抗性前列腺癌 （CRPC） 患者中，这是治疗耐药的机制，并且与侵袭性疾病和不良预后有关。NEPC 肿瘤通常显示小细胞癌形态，伴有雄激素受体 （AR） 表达缺失和神经内分泌 （NE） 谱系标志物增加。然而，在谱系可塑性过程中观察到一系列表型，混合组织学或共表达 AR 和 NE 标志物或缺乏所有标志物的组织学的临床意义尚不明确。调查 NEPC 的转化研究使用了可变定义，使临床试验设计具有挑战性。在这里，我们讨论了转移性活检的诊断性检查，以帮助指导表型 CRPC 亚型的可重复分类。我们建议根据组织形态学（腺癌、小细胞癌、低分化癌、其他形态学变异或混合形态学）和免疫组织化学标志物对 CRPC 肿瘤进行分类，优先考虑 AR、NKX3.1、INSM1、突触素和基于 Ki-67 阳性的细胞增殖，并根据临床情况考虑其他标志物。最终，转移性 CRPC 活检的统一检查可以改进临床试验设计和最终实践。