PO.CL01.20 · 临床研究

转移性去势抵抗性前列腺癌活检中组织形态学和免疫组化特征的系统性评估

Systematic assessment of histomorphologic and immunohistochemical features in metastatic castration-resistant prostate cancer biopsies

编号 3826 展板 10 时间 4/20 02:00–05:00 区域 Section 44 主讲 Elnaz Mahmoudabadi, MD

分会场 Diagnostic Biomarkers 1

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作者与单位 Authors & Affiliations

Elnaz Mahmoudabadi¹, Erolcan Sayar¹, Peter S. Nelson¹, Michael Schweizer², Funda Vakar-Lopez³, Lawrence True³, Jakob Valk³, Maria Tretiakova³, Nancy Y. Greenland⁴, Deepika Sirohi⁴, Bradley A. Stohr⁴, Jeffry P. Simko⁴, Michael C. Haffner¹, Chien-Kuang Cornelia Ding⁴

¹Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA,²Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA,³Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA,⁴Department of Pathology, University of California San Francisco, San Francisco, CA

摘要 Abstract

中文摘要

背景：转移性去势抵抗性前列腺癌（mCRPC）代表一种异质性的疾病谱。虽然许多肿瘤仍由雄激素受体（AR）驱动，但另一些则向神经内分泌前列腺癌（NEPC）发生谱系可塑性转变。中间型或混合型表型——例如AR与神经内分泌（NE）标志物共表达或缺乏所有谱系标志物的肿瘤——的意义仍未得到明确界定。我们试图对真实世界的mCRPC活检进行组织形态学和免疫组化（IHC）的系统性表征。方法：回顾性审阅了来自两家机构的117份mCRPC活检，并依据H&E染色上的肿瘤形态进行分类。针对NKX3.1、AR、突触素（SYP）、胰岛素瘤相关蛋白1（INSM1）和Ki-67进行了IHC检测。使用H评分（0-300）对表达进行半定量评分，Ki-67以肿瘤细胞核阳性染色的百分比报告。结果：组织学分布包括44例腺癌、53例低分化癌、15例NEPC和5例混合亚型。以H评分>40为阈值，腺癌常表达NKX3.1（93%）和AR（100%），而NE标志物表达有限（INSM1为13%，SYP为46%）。低分化癌最常保留NKX3.1（80%）和AR（84%），而NE标志物表达较少见（SYP 27%，INSM1 26%）。混合型肿瘤在各谱系间表现出共表达（AR 100%，NKX3.1 100%，SYP 80%，INSM1 50%）。NEPC表现出弥漫性NE分化（SYP 85%，INSM1 75%），NKX3.1或AR阳性罕见（分别为8%和0%）。高H评分（>200）在NKX3.1（83%）和AR（92%）阳性的腺癌中富集，而大多数NEPC表现出高SYP表达和高Ki-67增殖指数。在1例低分化癌和2例NEPC中，所有四种IHC标志物均见低H评分（<40）。结论：本研究提供了对mCRPC活检形态学和IHC标志物表达的首批系统性、标准化评估之一。NKX3.1和AR在腺癌和低分化癌中占主导，而SYP和INSM1可可靠地识别神经内分泌癌。混合亚型表现出重叠的谱系特征。Ki-67提示各亚型间肿瘤增殖存在差异。这些发现凸显了mCRPC的形态学和免疫表型异质性，并强调需要进行整合性病理评估以完善诊断并支持转化研究。

查看英文原文 English abstract

Background: Metastatic castration-resistant prostate cancer (mCRPC) represents a heterogeneous disease spectrum. While many tumors remain androgen receptor (AR)-driven, others undergo lineage plasticity toward neuroendocrine prostate cancer (NEPC). The significance of intermediate or mixed phenotypes-such as tumors with co-expression of AR and neuroendocrine (NE) markers or lacking all lineage markers-remains poorly defined. We sought to systematically characterize histomorphology and immunohistochemistry (IHC) in real-world mCRPC biopsies. Methods: 117 mCRPC biopsies from two institutions were retrospectively reviewed and classified by tumor morphology on H&E. IHC was performed for NKX3.1, AR, synaptophysin (SYP), insulinoma-associated protein 1 (INSM1), and Ki-67. Expression was semi-quantitatively scored using H-scores (0-300), and Ki-67 was reported as the percentage of tumor nuclei with positive staining. Results: Histologic distribution included 44 adenocarcinomas, 53 poorly differentiated carcinomas, 15 NEPC, and 5 mixed subtypes. Using H-score >40 as a cutoff, adenocarcinomas frequently expressed NKX3.1 (93%) and AR (100%), with limited NE marker expression (13% for INSM1 and 46% for SYP). Poorly differentiated carcinomas most often retained NKX3.1 (80%) and AR (84%), while NE marker expression was less common (SYP 27%, INSM1 26%). Mixed tumors demonstrated co-expression across lineages, (AR 100%, NKX3.1 100%, SYP 80%, INSM1 50%). NEPC showed diffuse NE differentiation (SYP 85%, INSM1 75%) with rare NKX3.1 or AR positivity (8% and 0%, respectively). High H-scores (>200) were enriched in NKX3.1 (83%) and AR (92%) positive adenocarcinomas, while majority NEPC showed high SYP expression and high Ki-67 proliferation index. Low H-score (<40) are seen across all four IHC markers in 1 poorly differentiated carcinoma and 2 NEPC. Conclusions: This study provides one of the first systematic, standardized assessments of mCRPC biopsy morphology and IHC marker expression. NKX3.1 and AR predominated in adenocarcinoma and poorly differentiated carcinomas, whereas SYP and INSM1 reliably identified neuroendocrine carcinomas. Mixed subtypes exhibited overlapping lineage features. Ki-67 indicated differences in tumor proliferation across subtypes. These findings highlight the morphologic and immunophenotypic heterogeneity of mCRPC and emphasize the need for integrated pathologic evaluation to refine diagnosis and support translational research.

利益披露 Disclosure

E. Mahmoudabadi, None.. E. Sayar, None.. P. S. Nelson, None. M. Schweizer, Janssen ). Pfizer ). Novartis ). Zenith Epigenetics ). BMS ). Merck ). Epigenetix ). Xencor ). Ambrx ). Oric Pharmaceuticals ). AstraZeneca ). Lightspeed ). Fibrogen ). Daiichi Sankyo ). K36 Therapeutics ). F. Vakar-Lopez, None.. L. True, None.. J. Valk, None.. M. Tretiakova, None.. N. Y. Greenland, None.. D. Sirohi, None. B. A. Stohr, Alessa Therapeutics Stock, Other. J. P. Simko, None. M. C. Haffner, Pfizer ). Astra Zeneca ). Merck ). Novartis ). Genentech ). Promicell ). Bristol Myers Squibb ). C. Ding, Bristol Myers Squibb Foundation ). Intuitive Surgical ). Merck ).

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