孤立性纤维瘤的免疫肿瘤微环境——将免疫浸润与具有预后意义的变量相关联

Immunological Tumor Microenvironment of Solitary Fibrous Tumors-Associating Immune Infiltrate with Variables of Prognostic Significance.

作者信息

Medina-Ceballos Emilio, Machado Isidro, Giner Francisco, Blázquez-Bujeda Álvaro, Espino Mónica, Navarro Samuel, Llombart-Bosch Antonio

机构信息

Pathology Department, Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain.

Pathology Department, Instituto Valenciano de Oncología, 46009 Valencia, Spain.

出版信息

Cancers (Basel). 2024 Sep 21;16(18):3222. doi: 10.3390/cancers16183222.

DOI:10.3390/cancers16183222

PMID:39335193

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11430690/

Abstract

BACKGROUND AND OBJECTIVES

Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs).

METHODS

A retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10-49, 2 = 50-99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round-oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS.

RESULTS

Only one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round-oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1.

CONCLUSIONS

SFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores.

摘要

背景与目的

孤立性纤维瘤（SFTs）是形态学上异质性的肿瘤，其特征为基因融合。临床结果可能差异很大，虽然大多数病例预后良好，但有些可能进展为侵袭性疾病，表现为复发和转移，最终导致患者死亡。在此，我们分析SFTs的免疫肿瘤微环境（ITME），旨在确定其预后价值以及与既定风险分层系统（RSSs）的相关性。

方法

一项对52例经融合确认且有临床随访数据的SFTs进行的回顾性观察多中心研究。在组织微阵列中评估免疫组织化学分析，包括CD163、CD68、CD3、CD8、CD20、PDL-1、PD-1和LAG1，使用模拟评分，分数范围为0至3（0 =≤9，1 = 10 - 49，2 = 50 - 99，3 =每10个高倍视野中阳性细胞>100）。这些标志物的表达与临床结果、先前在全玻片组织切片中评估的形态学特征（细胞丰富/细胞稀少、圆形-椭圆形或梭形为主的组成细胞（DCC）形态以及坏死）、Ki67、总生存期和RSS相关。

结果

所研究的52例病例中仅1例出现进展。在多变量分析中，免疫细胞（B淋巴细胞、T淋巴细胞和巨噬细胞）的存在与否均与评估出的RSSs（德米科、杉田、G评分和黄氏评分）无任何关联。有趣的是，出现进展的病例免疫浸润程度高，CD68、CD163、CD8和CD20标志物表达（评分为3）。圆形-椭圆形细胞形态与较高水平的CD163巨噬细胞的存在相关。最后，CD20 +淋巴细胞的少量存在与较少的坏死相关，而PDL-1表达较高的病例与Ki67值增加相关。所有病例LAG-1和PD-1均为阴性。