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基于肿瘤芽基分级的 HPV 阳性和 HPV 阴性头颈部肿瘤独立预后生物标志物。

Tumour budding-based grading as independent prognostic biomarker in HPV-positive and HPV-negative head and neck cancer.

机构信息

Institute of Pathology, School of Medicine, Technical University of Munich (TUM), 81675, Munich, Germany.

University of Heidelberg, Institute of Pathology, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.

出版信息

Br J Cancer. 2023 Jun;128(12):2295-2306. doi: 10.1038/s41416-023-02240-y. Epub 2023 Apr 12.

DOI:10.1038/s41416-023-02240-y
PMID:37045906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10241901/
Abstract

BACKGROUND

The prognostic significance of tumour budding (TB) and minimal cell nest size (MCNS) was shown in human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC). However, the optimisation of cutpoints, the prognostic impact in HPV-positive HNSCC, and the comparison with other histopathological grading systems are insufficiently investigated.

METHODS

TB and MCNS were analysed digitally in 1 and 10 high-power fields (HPF) of 331 HPV-positive and HPV-negative cases from TCGA. Optimising the cutpoints a new cellular dissociation grading (CDG) system was defined and compared to the WHO grading and the Brandwein-Gensler (BG) risk model.

RESULTS

The two-tiered CDG system based solely on TB yielded optimal prognostic stratification with shortened overall survival for CDG-high cases. Optimal cut-offs were two buds (1 HPF) and six buds (10 HPF), respectively. Analysing MCNS did not add prognostic significance to quantifying TB. CDG was a significant prognostic marker in HPV-negative and HPV-positive tumours and prognostically superior to the WHO and BG systems. High CDG was associated with clinically occult lymph-node metastases.

CONCLUSIONS

The most comprehensive study of TB in HNSCC so far confirmed its prognostic impact in HPV-negative tumours and for the first time in HPV-positive tumours. Further studies are warranted to evaluate its applicability for therapy guidance in HNSCC.

摘要

背景

肿瘤芽（TB）和最小细胞巢大小（MCNS）的预后意义已在人乳头瘤病毒（HPV）阴性的头颈部鳞状细胞癌（HNSCC）中得到证实。然而，在 HPV 阳性的 HNSCC 中，对切点的优化、对预后的影响以及与其他组织病理学分级系统的比较仍研究不足。

方法

TCGA 中的 331 例 HPV 阳性和 HPV 阴性病例的 1 个和 10 个高倍视野（HPF）中进行了 TB 和 MCNS 的数字分析。通过优化切点，定义了一种新的细胞分离分级（CDG）系统，并与世界卫生组织（WHO）分级和 Brandwein-Gensler（BG）风险模型进行了比较。

结果

基于 TB 的两等级 CDG 系统可实现最佳的预后分层，CDG 高病例的总生存时间缩短。最佳截断值分别为 2 个芽（1 HPF）和 6 个芽（10 HPF）。分析 MCNS 并不能增加 TB 定量的预后意义。CDG 是 HPV 阴性和 HPV 阳性肿瘤的显著预后标志物，且在预后方面优于 WHO 和 BG 系统。高 CDG 与临床隐匿性淋巴结转移相关。

结论

迄今为止，对 HNSCC 中 TB 的最全面研究证实了其在 HPV 阴性肿瘤中的预后意义，并且首次在 HPV 阳性肿瘤中得到证实。需要进一步的研究来评估其在 HNSCC 治疗指导中的适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/5392b53ee8f2/41416_2023_2240_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/f5bf30ca742f/41416_2023_2240_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/d7121f02c9ca/41416_2023_2240_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/97263256bd70/41416_2023_2240_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/1e884e3290a4/41416_2023_2240_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/25ad99fe063f/41416_2023_2240_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/5392b53ee8f2/41416_2023_2240_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/f5bf30ca742f/41416_2023_2240_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/d7121f02c9ca/41416_2023_2240_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/97263256bd70/41416_2023_2240_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/1e884e3290a4/41416_2023_2240_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/25ad99fe063f/41416_2023_2240_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9d/10241901/5392b53ee8f2/41416_2023_2240_Fig6_HTML.jpg

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