PO.MCB11.01 · 分子与细胞生物学

p53免疫组化模式在1,515例头颈部鳞状细胞癌患者中的原发部位特异性分布及预后意义

Primary site specific distribution and prognostic significance of p53 immunohistochemistry patterns in 1,515 patients with head and neck squamous cell carcinoma

编号 602 展板 7 时间 4/19 02:00–05:00 区域 Section 25 主讲 Takane Watanabe

分会场 Tumor Suppressors

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作者与单位 Authors & Affiliations

Takane Watanabe¹, Yoshitaka Honma², Toshihide Ueno³, Yukiko Nakamura², Eijitsu Ryo⁴, Hideaki Takahashi², Akiko Mori⁵, Yuko Kubo⁶, Mitsuhiko Katoh⁷, Kohtaro Eguchi⁷, Azusa Sakai⁷, Toshihiko Sakai⁷, Chihiro Fushimi⁷, Go Omura⁷, Kenji Okami¹, Yasushi Yatabe⁸, Hiroyuki Mano³, Seiichi Yoshimoto⁷, Taisuke Mori⁸

¹Otorhinolaryngology/Head and Neck Surgery, Tokai University Hospital, Isehara, Japan,²Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan,³Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan,⁴Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan,⁵Dental Surgery, National Cancer Center Hospital, Tokyo, Japan,⁶Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan,⁷Head and Neck Surgery, National Cancer Center Hospital, Tokyo, Japan,⁸Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan

摘要 Abstract

中文摘要

背景：头颈部鳞状细胞癌（HNSCC）的特征是TP53突变高发，在癌症基因组图谱（TCGA）中约70%的病例存在该突变。尽管既往提示TP53突变发生率及相关临床行为存在原发部位特异性差异，但TCGA队列偏向于某些原发部位——尤其是口腔和喉部——对口咽和下咽肿瘤的代表性有限。为解决这一抽样偏倚，我们旨在利用大型机构队列中全面的p53免疫组化（IHC）阐明HNSCC的发生率、解剖分布及其预后意义。方法：我们回顾性分析了2013年至2023年间在国立癌症中心医院接受活检或手术的1,515例HNSCC患者。TP53状态根据p53-IHC模式（野生型、缺失型或蓄积型）推断，并进行p16-IHC以评估HPV相关性。采用Fisher精确检验和比值比（OR）评估原发部位特异性和亚部位特异性发生率模式。在排除原位癌、最佳支持治疗和外院治疗病例后，对1,364例患者评估了总生存期（OS）和疾病特异性生存期（DSS）。结果：在1,515例HNSCC病例中，409例（27.0%）被归类为p53野生型，736例（48.6%）为蓄积型，370例（24.4%）为缺失型。p53突变型肿瘤的发生率在各解剖部位间差异显著。突变富集的原发部位包括下咽/颈段食管（OR = 5.10，95% CI：3.49-7.46，p < 0.01）、喉部（OR = 1.88，95% CI：1.22-2.88，p < 0.01）和口腔（OR = 1.54，95% CI：1.19-2.00，p < 0.01）。相比之下，p53野生型肿瘤在口咽（OR = 0.25，95% CI：0.19-0.33，p < 0.01）和鼻咽（OR = 0.24，95% CI：0.13-0.47，p < 0.01）中显著多见。生存分析显示，p53 IHC野生型组的预后较突变型组显著改善（中位OS：未达到 vs. 110个月；HR = 0.59，95% CI：0.46-0.76，p < 0.01；中位DSS：两组均未达到；HR = 0.65，95% CI：0.47-0.89，p = 0.01）。结论：这项大型队列研究表明，HNSCC中p53改变模式存在显著的原发部位特异性变异，IHC p53突变型肿瘤在下咽和喉部明显富集，而p53 IHC野生型肿瘤在口咽癌、鼻咽癌和牙龈癌中富集。p53 IHC野生型模式始终与显著更好的生存相关。这些发现凸显了在解读TP53状态时考虑解剖亚部位背景的重要性，并提示p53 IHC可作为HNSCC中一种稳健且具临床相关性的生物标志物。

查看英文原文 English abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by a high prevalence of TP53 mutations, reported in approximately 70% of cases in The Cancer Genome Atlas (TCGA). Although primary site-specific variation in TP53 mutation prevalence and related clinical behavior has been suggested, the TCGA cohort is biased toward certain primary sites-particularly the oral cavity and larynx-with limited representation of oropharyngeal and hypopharyngeal tumors. To address this sampling bias, we aimed to clarify the prevalence and anatomical distribution of HNSCC, as well as its prognostic implications, using comprehensive p53 immunohistochemistry (IHC) in a large institutional cohort. Methods: We retrospectively analyzed 1,515 patients with HNSCC who underwent biopsy or surgery at the National Cancer Center Hospital between 2013 and 2023. TP53 status was inferred from p53-IHC patterns (wild-type, lost-type, or accumulation-type), and p16-IHC was performed to assess HPV association. Primary site-specific and subsite-specific prevalence patterns were evaluated using Fisher's exact test and odds ratios (ORs). Overall survival (OS) and disease-specific survival (DSS) were assessed in 1,364 patients after excluding carcinoma in situ, best supportive care, and outside-treated cases. Results: Among 1,515 HNSCC cases, 409 (27.0%) were classified as p53 wild-type, 736 (48.6%) as accumulation-type, and 370 (24.4%) as lost-type. The prevalence of p53 mutated-type tumors varied markedly across anatomical sites. Mutation-enriched primary sites included the hypopharynx/cervical esophagus (OR = 5.10, 95% CI: 3.49-7.46, p < 0.01), larynx (OR = 1.88, 95% CI: 1.22-2.88, p < 0.01), and oral cavity (OR = 1.54, 95% CI: 1.19-2.00, p < 0.01). In contrast, p53 wild-type tumors were significantly frequent in the oropharynx (OR = 0.25, 95% CI: 0.19-0.33, p < 0.01) and nasopharynx (OR = 0.24, 95% CI: 0.13-0.47, p < 0.01). Survival analysis revealed significantly improved outcomes in the p53 IHC wild-type group compared with the mutated-type group (median OS: not reached vs. 110 months; HR = 0.59, 95% CI: 0.46-0.76, p < 0.01; median DSS: both not reached; HR = 0.65, 95% CI: 0.47-0.89, p = 0.01). Conclusion: This large cohort study demonstrates substantial primary site-specific variation in p53 alteration patterns across HNSCC, with notable enrichment of IHC p53-mutated tumors in the hypopharynx and larynx, and enrichment of p53 IHC wild-type tumors in oropharyngeal, nasopharyngeal, and gingival cancers. The p53 IHC wild-type pattern was consistently associated with significantly better survival. These findings highlight the importance of anatomical subsite context when interpreting TP53 status and suggest that p53 IHC serves as a robust, clinically relevant biomarker in HNSCC.

利益披露 Disclosure

T. Watanabe, None.. Y. Honma, None.. T. Ueno, None.. Y. Nakamura, None.. E. Ryo, None.. H. Takahashi, None.. A. Mori, None.. Y. Kubo, None.. M. Katoh, None.. K. Eguchi, None.. A. Sakai, None.. T. Sakai, None.. C. Fushimi, None.. G. Omura, None.. K. Okami, None.. Y. Yatabe, None.. H. Mano, None.. S. Yoshimoto, None.. T. Mori, None.

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