同步性头颈部癌和食管癌与异时性头颈部癌和食管癌之间免疫和 TP53 突变表型的差异。

The differences of immunologic and TP53 mutant phenotypes between synchronous and metachronous head and neck cancer and esophageal cancer.

机构信息

Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.

Department of Pathology, National Taiwan University Hospital, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Oral Oncol. 2020 Dec;111:104945. doi: 10.1016/j.oraloncology.2020.104945. Epub 2020 Aug 5.

DOI:10.1016/j.oraloncology.2020.104945

PMID:32769036

Abstract

OBJECTIVE

To determine the tumor genomic, immunologic expression, and risk factors of treatment outcomes for patients with double head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC).

METHODS

We reviewed patients with double HNSCC and ESCC between 1995 and 2014. The TP53 genomic mutation, CD8+ tumor infiltrating lymphocytes (TIL) and tumor programmed cell death ligand 1 (PD-L1) expression of paired HNSCC and ESCC were analyzed.

RESULTS

A total of 116 patients (57 metachronous and 59 synchronous) were included. There were 88 (75.86%) patients with HNSCC and 80 (68.97%) with ESCC harboured TP53 disruptive mutation. Nearly 106 (91.38%) patients had different clonality of TP53 mutation in paired HNSCC and ESCC. The immunologic expression of synchronous and metachronous patients was significantly different. Compared to the metachronous patients, the synchronous patients had significantly higher HNSCC CD8+ TIL (p = 0.03), ESCC CD8+ TIL (p < 0.001), HNSCC PD-L1+ tumor proportion score (TPS, p = 0.04), and ESCC PD-L1+ TPS (p = 0.04). Furthermore, among the synchronous patients, the immunologic expression between HNSCC and ESCC was significantly correlated. The CD8+ TIL and PD-L1 TPS had strongly (r = 0.63, p < 0.0001) and moderately (r = 0.42, p = 0.001) positive correlations, respectively. Finally, advanced stage (III/IV) HNSCC was a significant factor for disease-free (p = 0.03) and overall survival (p = 0.005).

CONCLUSION

In patients with double HNSCC and ESCC, nearly all HNSCC and ESCC were of multicentric origin. For the synchronous patients, there was more adaptive immune resistance in HNSCC and ESCC. The immunologic expression between paired HNSCC and ESCC was also significantly correlated.

摘要

目的

确定双头颈鳞状细胞癌（HNSCC）和食管鳞状细胞癌（ESCC）患者的肿瘤基因组、免疫表达和治疗结果的危险因素。

方法

我们回顾了 1995 年至 2014 年间患有双 HNSCC 和 ESCC 的患者。分析了配对 HNSCC 和 ESCC 的 TP53 基因组突变、CD8+肿瘤浸润淋巴细胞（TIL）和肿瘤程序性死亡配体 1（PD-L1）表达。

结果

共纳入 116 例患者（57 例为异时性，59 例为同期性）。88 例（75.86%）HNSCC 和 80 例（68.97%）ESCC 患者存在 TP53 破坏性突变。近 106 例（91.38%）患者在配对 HNSCC 和 ESCC 中具有不同的 TP53 突变克隆性。同期和异时性患者的免疫表达存在显著差异。与异时性患者相比，同期性患者的 HNSCC CD8+TIL（p=0.03）、ESCC CD8+TIL（p<0.001）、HNSCC PD-L1+肿瘤比例评分（TPS，p=0.04）和 ESCC PD-L1+TPS（p=0.04）显著升高。此外，在同期性患者中，HNSCC 和 ESCC 之间的免疫表达呈显著相关性。CD8+TIL 和 PD-L1 TPS 具有很强的（r=0.63，p<0.0001）和中度（r=0.42，p=0.001）正相关性。最后，晚期（III/IV 期）HNSCC 是无病生存（p=0.03）和总生存（p=0.005）的显著因素。