鼻窦内翻性乳头状瘤和鳞状细胞癌中的 EGFR 突变和 HPV 感染。

EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma.

机构信息

Dept Head and Neck Oncology, Instituto de Investigacion Sanitaria del Principado de Asturias, Oviedo, Spain.

Dept Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.

出版信息

Rhinology. 2020 Aug 1;58(4):368-376. doi: 10.4193/Rhin19.371.

DOI:10.4193/Rhin19.371

PMID:32199023

Abstract

BACKGROUND

To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment.

METHODS

We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data.

RESULTS

We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC.

CONCLUSIONS

EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

摘要

背景

评估 EGFR 信号通路和 HPV 感染在一组内翻性鼻窦乳头状瘤（ISP）和鼻窦鳞状细胞癌（SNSCC）中的作用，及其对预后和临床治疗的价值。

方法

我们分析了 55 例 ISP、14 例与 ISP 相关的 SNSCC（SNSCC-isp）和 60 例与 ISP 不相关的 SNSCC（SNSCC-novo）的 EGFR 基因突变和拷贝数增加、EGFR 蛋白表达和磷酸化 EGFR（pEGFR）以及 HPV 感染和 KRAS 突变情况。将发现结果与临床病理和随访数据相关联。

结果

我们发现 38%（7/18）的 ISP、50%（6/12）的 SNSCC-isp 和 5%（1/19）的 SNSCC-novo 存在 EGFR 外显子 20 突变。92%的 ISP 表达 EGFR，而 54%（21/39）的 ISP 存在 pEGFR。SNSCC-isp 和 SNSCC-novo 表现出相似的 EGFR（57%和 33%）和 pEGFR（44%和 38%）表达。我们观察到 EGFR 外显子 20 突变和 pEGFR 表达之间存在反比关系。39 例 ISP 中有 4 例（10%）携带 HPV-16。12 例 SNSCC-isp 中有 3 例（25%）和 8 例 SNSCC-novo 中有 1 例（13%）检测到致癌性 HPV。在任何样本中均未检测到 KRAS 突变。HPV 感染与 pEGFR 表达呈负相关，但与 EGFR 突变无关。通过突变或磷酸化激活 EGFR 的 ISP 具有更长的 ISP 无复发生存期，然而，无论是 EGFR 外显子 20 突变、pEGFR 表达还是 HPV 感染，在 SNSCC 中均未显示出预后价值。