髓母细胞瘤分子分层的免疫组织化学替代物。

IF 1.3 4区 医学 Q3 ANATOMY & MORPHOLOGY Applied Immunohistochemistry & Molecular Morphology Pub Date : 2023-09-01 Epub Date: 2023-07-21 DOI:10.1097/PAI.0000000000001143
Dheeraj Chinnam, Aastha Saraswati, Swathi Jogunoori, Aanchal Verma, Tanvi Kiran, Pravin Salunke, Nalini Gupta, Narendra Kumar, Renu Madan, Bishan Dass Radotra, Kirti Gupta
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引用次数: 0

摘要

背景:世界卫生组织中枢神经系统肿瘤分类(2016)识别了髓母细胞瘤(MB)中的4种组织学变异和遗传定义的分子亚群。此外,在2021年的分类中,在反映生物多样性的现有亚组中暂时增加了新的亚型。YAP1、GAB1和β-连环蛋白通常被认为是鉴定这些遗传亚群的替代标记。目的:我们旨在使用3种免疫组织化学标记物将MB分为分子亚组。TP53突变也在Wingless(WNT)和Sonic Hedgehog(SHH)亚组中进行了评估。在这些分子亚组中比较人口统计学特征、影像学细节和生存结果。患者和方法:我们的队列包括过去10年中诊断的164例MB病例。在组织学上鉴定组织学变异,并使用YAP1、GAB1和β-连环蛋白对肿瘤进行分子分层。此外,在WNT和SHH亚组中使用免疫组织化学评估TP53突变。从记录中检索临床细节和生存结果,并对上述相关性进行统计学评估。结果:患者年龄1~52岁,男女比例为2:1。第3组/第4组占大多数(48.4%),其次是SHH(45.9%)和WNT亚组(5.7%)。结节性/结节性和广泛结节性MB的存活率最高,而大细胞/间变性的存活率最差。随访时间为1-129个月。WNT亚组的疗效最好,其次是SHH亚组;第3组/第4组最差。在SHH亚组中,与SHH-TP53野生型相比,TP53突变型肿瘤的预后明显较差。结论:分子分层有助于预测,在先进分子检测有限的中心,一组3种抗体有助于将MB分为其亚组。我们的研究加强了将这种成本效益高、最小的小组纳入常规分层实践的有效性。此外,我们提出了一个3风险分层分组,结合形态学和分子标记。
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Immunohistochemical Surrogates for Molecular Stratification in Medulloblastoma.

Background: The WHO classification of central nervous system neoplasms (2016) recognized 4 histologic variants and genetically defined molecular subgroups within medulloblastoma (MB). Further, in the 2021 classification, new subtypes have been provisionally added within the existing subgroups reflecting the biological diversity. YAP1, GAB1, and β-catenin were conventionally accepted as surrogate markers to identify these genetic subgroups.

Objectives: We aimed to stratify MB into molecular subgroups using 3 immunohistochemical markers. TP53 mutation was also assessed in Wingless (WNT), and Sonic Hedgehog (SHH) subgroups. Demographic profiles, imaging details, and survival outcomes were compared within these molecular subgroups.

Patients and methods: Our cohort included 164 MB cases diagnosed over the last 10 years. The histologic variants were identified on histology, and tumors were molecularly stratified using YAP1, GAB1, and β-catenin. Further, TP53 mutation was assessed using immunohistochemical in WNT and SHH subgroups. The clinical details and survival outcomes were retrieved from the records, and the mentioned correlates were evaluated statistically.

Results: The age ranged from 1 to 52 years with M:F ratio of 2:1. Group 3/group 4 constituted the majority (48.4%), followed by SHH (45.9%) and WNT subgroups (5.7%). Desmoplastic/nodular and MB with extensive nodularity had the best survival, whereas large cell/anaplastic had the worst. The follow-up period ranged from 1 to 129 months. The best outcome was observed for the WNT subgroup, followed by the SHH subgroup; group 3/group 4 had the worst. Among the SHH subgroup, TP53 mutant tumors had a significantly poorer outcome compared with SHH-TP53 wildtype.

Conclusions: Molecular stratification significantly contributes to prognostication, and a panel of 3 antibodies is helpful in stratifying MB into its subgroups in centers where access to advanced molecular testing is limited. Our study reinforces the efficacy of incorporating this cost-effective, minimal panel into routine practice for stratification. Further, we propose a 3-risk stratification grouping, incorporating morphology and molecular markers.

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来源期刊
Applied Immunohistochemistry & Molecular Morphology
Applied Immunohistochemistry & Molecular Morphology ANATOMY & MORPHOLOGY-MEDICAL LABORATORY TECHNOLOGY
CiteScore
3.20
自引率
0.00%
发文量
153
期刊介绍: ​Applied Immunohistochemistry & Molecular Morphology covers newly developed identification and detection technologies, and their applications in research and diagnosis for the applied immunohistochemist & molecular Morphologist. Official Journal of the International Society for Immunohistochemisty and Molecular Morphology​.
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