Pathological and Clinical Implications of Tumor Microenvironment Evaluated With Multiplex Immunohistochemistry in Testicular Embryonal Carcinoma

IF 2.4 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI:10.1016/j.clgc.2025.102444

Valentina Tateo , Costantino Ricci , Sofia Melotti , Elisa Tassinari , Matteo Rosellini , Andrea Marchetti , Linda Danielli , Antonio Maestri , Andrea Necchi , Veronica Mollica , Michelangelo Fiorentino , Francesco Massari

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引用次数: 0

Abstract

Introduction

Testicular germ cell tumors (TGCTs) are the most common cancer in young men. Their development is closely linked to embryogenesis, yet much about their pathogenesis remains unknown. TGCTs exhibit exceptional sensitivity to cisplatin-based chemotherapy, achieving high cure rates even in metastatic disease. Further research is needed to deepen our understanding of TGCTs and refine risk stratification. In this pilot study, we focused on embryonal carcinoma (EC), a subtype with increased risk of relapse and considered a key step in TGCT reprogramming.

Patients and Methods

We analyzed the tumor microenvironment (TME) in 49 EC samples using bright-field multiplex immunohistochemistry (BF-mIHC), which enables the simultaneous evaluation of multiple biomarkers, making it particularly useful for TME characterization. We evaluated B-cells (CD20), T-cells (CD3), and tumor-associated macrophages (TAMs, CD68) and established cutoffs that correlated with reprogramming phase, clinical stage, and relapse.

Results

High TAM levels (CD68 + > 83/mm²) were strongly associated with phase I of reprogramming (pure EC or EC mixed only with seminoma), while low TAM characterized phase II (P < .001), suggesting a role in stemness maintenance through epigenetic regulation. High CD68 (> 46/mm²) and CD3 (> 125.5/mm²) correlated with metastatic disease (P < .001 and P = .026, respectively), whereas high CD20 (> 38.5/mm²) and CD3 (> 83/mm²) were linked to lower relapse risk (P = .014 and P = .017, respectively). Important limits are small sample size and few relapse events.

Conclusions

These findings highlight the relevance of TME in TGCT biology and prognosis. The observed associations suggest TME may influence tumor plasticity, metastatization and relapse risk, warranting validation in larger studies.

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多重免疫组化评价睾丸胚胎癌肿瘤微环境的病理和临床意义。

睾丸生殖细胞肿瘤（tgct）是年轻男性最常见的癌症。它们的发育与胚胎发生密切相关，但其发病机制尚不清楚。tgct对以顺铂为基础的化疗表现出异常的敏感性，即使在转移性疾病中也能实现高治愈率。需要进一步的研究来加深我们对tgct的理解并完善风险分层。在这项初步研究中，我们关注胚胎癌（EC），这是一种复发风险增加的亚型，被认为是TGCT重编程的关键步骤。患者和方法：我们使用亮场多重免疫组织化学（BF-mIHC）分析了49例EC样本的肿瘤微环境（TME），该方法可以同时评估多种生物标志物，使其对TME表征特别有用。我们评估了b细胞（CD20）、t细胞（CD3）和肿瘤相关巨噬细胞（tam、CD68），并建立了与重编程阶段、临床阶段和复发相关的截止点。结果：高TAM水平（CD68 + bbb83 /mm²）与I期重编程（纯EC或EC仅与精原细胞瘤混合）密切相关，而低TAM特征的II期（p46 /mm²）和CD3 （>25.5 /mm²）与转移性疾病相关（p38.5 /mm²）和CD3 （>25.5 /mm²）与较低的复发风险相关（P= 0.014和P= 0.017）。重要的限制是样本量小，复发事件少。结论：这些发现突出了TME与TGCT生物学和预后的相关性。观察到的关联表明，TME可能影响肿瘤的可塑性、转移和复发风险，需要在更大规模的研究中进行验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical genitourinary cancer 医学-泌尿学与肾脏学

CiteScore

5.20

自引率

6.20%

发文量

201

审稿时长

54 days

期刊介绍： Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.