子宫内膜细胞学能否识别出免疫疗法的受益患者?

IF 1.6 4区 医学 Q3 PATHOLOGY Acta Cytologica Pub Date : 2024-01-01 Epub Date: 2024-03-12 DOI:10.1159/000538288
Shintaro Yanazume, Yukari Kirita, Yusuke Kobayashi, Ikumi Kitazono, Toshiaki Akahane, Mika Mizuno, Shinichi Togami, Akihide Tanimoto, Hiroaki Kobayashi
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引用次数: 0

摘要

导言:根据癌症基因组图谱(TCGA)的分类,POLE(聚合酶epsilon)突变(POLEmut)亚型、MMR缺陷(MMR-d)亚型和高肿瘤突变负荷(TMB-high)患者可能从免疫疗法中获益。然而,这些人群的细胞学形态特征仍然未知:方法:对从福尔马林固定石蜡包埋组织中提取的DNA进行新一代测序分析。分析了与妇科癌症、TMB和微卫星不稳定性(MSI)相关的基因组突变,并将其归入TCGA的四种分类类型。在开始初始治疗前,采用液基制备法对子宫内膜癌进行了以下形态学细胞学检查:i)细胞学背景;ii)中性粒细胞和淋巴细胞各计数之间的差异,如下所述:结果:TCGA 组的细胞学背景模式与 TMB 状态无显著差异。虽然 TCGA 组的中性粒细胞计数无显著差异(p= 0.955),但 POLEmut 和 MMR-d 的淋巴细胞计数显著高于无特异性分子谱(NSMP)(p= 0.019 和 0.037,分别为 0.019 和 0.037);此外,p53mut 也有显著差异的趋势(p= 0.064)。TMB高的淋巴细胞计数也明显高于TMB低的(p= 0.002)。POLEmut 与 TMB 水平和淋巴细胞计数呈正相关。在预测 POLEmut 加 MMR-d 患者时,淋巴细胞计数显示出更高的诊断准确性,曲线下面积(AUC)(0.70,95% CI:0.57-0.84),临界值为 26 个高倍视野(HPF):结论:使用液基细胞学方法对子宫内膜癌患者进行淋巴细胞计数,可预测TCGA组的POLEmut加MMR-d和TMB-high患者的免疫疗法受益情况。
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Can Endometrial Cytology Identify Patients Who Would Benefit from Immunotherapy?

Introduction: Patients with polymerase epsilon (POLE) mutation (POLEmut) subtype, MMR-deficient (MMR-d) subtype as classified by The Cancer Genome Atlas (TCGA), and a high tumor mutation burden (TMB-high) potentially benefit from immunotherapy. However, characteristics of the cytological morphology within these populations remain unknown.

Methods: DNA extracted from formalin-fixed paraffin-embedded tissues was subjected to next-generation sequencing analysis. Genomic mutations related to gynecological cancers, TMB, and microsatellite instability were analyzed and were placed in four TCGA classification types. The following morphological cytological investigations were conducted on endometrial cancer using a liquid-based preparation method, prior to the commencement of initial treatment: (i) cytological backgrounds; (ii) differences between each count of neutrophils and lymphocytes as described below.

Results: Insignificant differences in the cytological background patterns of TCGA groups and TMB status were found. Although there was no significant difference in neutrophil count (p = 0.955) in the TCGA groups, POLEmut and MMR-d had significantly higher lymphocyte counts than no specific molecular profile (NSMP) (p = 0.019 and 0.037, respectively); furthermore, p53mut also tended to be significant (p = 0.064). Lymphocyte counts in TMB-high were also significantly greater than TMB-low (p = 0.002). POLEmut showed a positive correlation between TMB levels and lymphocyte counts. For predicting patients with POLEmut plus MMR-d, lymphocyte counts demonstrated a superior diagnostic accuracy of area under the curve (AUC) (0.70, 95% CI: 0.57-0.84), with a cutoff value of 26 high-power field.

Conclusion: Lymphocyte count using liquid-based cytology for patients with endometrial cancer may predict POLEmut plus MMR-d of TCGA groups and TMB-high in those who can benefit from immunotherapy.

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来源期刊
Acta Cytologica
Acta Cytologica 生物-病理学
CiteScore
3.70
自引率
11.10%
发文量
46
审稿时长
4-8 weeks
期刊介绍: With articles offering an excellent balance between clinical cytology and cytopathology, ''Acta Cytologica'' fosters the understanding of the pathogenetic mechanisms behind cytomorphology and thus facilitates the translation of frontline research into clinical practice. As the official journal of the International Academy of Cytology and affiliated to over 50 national cytology societies around the world, ''Acta Cytologica'' evaluates new and existing diagnostic applications of scientific advances as well as their clinical correlations. Original papers, review articles, meta-analyses, novel insights from clinical practice, and letters to the editor cover topics from diagnostic cytopathology, gynecologic and non-gynecologic cytopathology to fine needle aspiration, molecular techniques and their diagnostic applications. As the perfect reference for practical use, ''Acta Cytologica'' addresses a multidisciplinary audience practicing clinical cytopathology, cell biology, oncology, interventional radiology, otorhinolaryngology, gastroenterology, urology, pulmonology and preventive medicine.
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