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子宫颈 I 期神经内分泌肿瘤中的免疫细胞密度、HLA 状态和 PD-L1 表达

英文原题:Immune cell densities, HLA status, and PD-L1 expression in stage I neuroendocrine neoplasm of the uterine cervix.

PubMed 2025/07/25(内容时间) Pathol Res Pract Q1 · IF 3.7(JCR 2025)

研究概要

仅3例为纯NENs,而13例包含腺癌或鳞状细胞癌成分。

中文摘要

子宫颈神经内分泌肿瘤(NENs)是高度恶性的肿瘤,预后较差。基于人乳头瘤病毒检测的子宫颈癌筛查方法能够发现早期子宫颈NENs,因此迫切需要针对最早期的治疗策略。本研究旨在探讨和评估I期子宫颈NENs中瘤内及间质免疫细胞密度,以及人类白细胞抗原(HLA)和程序性细胞死亡配体1(PD-L1)表达的预后意义。共鉴定出16例NENs,包括8例大细胞神经内分泌癌(LCNECs)、4例小细胞神经内分泌癌(SCNECs)、3例神经内分泌肿瘤(NETs)和1例伴有SCNEC成分的LCNEC。仅3例为单纯性NENs,而13例包含腺癌或鳞状细胞癌成分。16例患者中有8例发生术后复发。无复发组的瘤内CD3阳性和CD8阳性细胞密度显著高于复发组(中位密度:136 vs. 48 cells/mm 2,P = 0.0281;91 vs. 27 cells/mm 2,P = 0.0359)。两组之间在临床病理特征、其他免疫细胞密度或HLA I类、HLA-DR或PD-L1表达方面未观察到显著差异。HLA-DR表达在子宫颈NENs中几乎缺失,而邻近的非NEN成分则显示出不同程度的HLA-DR表达。25 %的病例中观察到PD-L1表达,伴有CD3阳性和CD8阳性T细胞丰富的间质。所观察到的肿瘤微环境改变可能为子宫颈NEN的未来治疗提供线索。(240/250词)。

展开英文摘要原文

Neuroendocrine neoplasms (NENs) of the uterine cervix are highly malignant tumors associated with a poor prognosis. Human papillomavirus test-based uterine cervical cancer screening methods can detect early-stage uterine cervical NENs, so therapeutic strategies for the earliest stages are urgently needed. This study aimed to investigate and evaluate the prognostic significance of intratumoral and stromal immune cell densities, as well as human leukocyte antigen (HLA) and programmed cell death ligand 1 (PD-L1) expression in stage I uterine cervical NENs. Sixteen NENs were identified, including 8 large cell neuroendocrine carcinomas (LCNECs), 4 small cell neuroendocrine carcinomas (SCNECs), 3 neuroendocrine tumors (NETs), and 1 LCNEC with an SCNEC component. Only 3 cases were pure NENs, while 13 cases included a component of adenocarcinoma or squamous cell carcinoma. Eight of the 16 patients experienced postoperative recurrence. The recurrence-free group exhibited significantly higher densities of intratumoral CD3- and CD8-positive cells compared to the recurrence group (median densities: 136 vs. 48 cells/mm 2 , P = 0.0281 and 91 vs. 27 cells/mm 2 , P = 0.0359, respectively). No significant differences in clinicopathological characteristics, other immune cell densities, or expression of HLA class I, HLA-DR, or PD-L1 were observed between groups. HLA-DR expression was nearly absent in uterine cervical NENs, whereas adjacent non-NEN components displayed varying degrees of HLA-DR expression. PD-L1 expression was observed in 25 % of cases, with CD3- and CD8-positive T-cell-rich stroma. The observed modifications to tumor microenvironments could offer clues to future treatments for uterine cervical NEN. (240/250 words).

论文信息

作者
Yamada R、Kawakami F、Maeda N、Nagao S、Yamamoto M、Motohara T、Kondoh E、Mikami Y
第一作者单位
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan.Japan
通讯作者单位
Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan; Department of Pathology and Cell Biology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. Electronic address: kwkmfm@kuhp.kyoto-u.ac.jp.Japan
期刊
Pathology, research and practice2025 Sep
原文标识
PubMed 40752446 · DOI 10.1016/j.prp.2025.156146