Department of Tumor Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, Poland.
Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, Poland.
Pol J Pathol. 2021;72(4):296-314. doi: 10.5114/pjp.2021.113073.
The aim of the study was to compare prognostic potential of PIK3CA mutations and expression of proteins involved in or regulate EGFR/PI3K/Akt/mTOR signaling in HPV16 positive and HPV negative head and neck squamous cell carcinoma (HNSCC) patients. The expression of proteins (EGFR, Akt, pAkt(Ser473), pAkt(Thr308), mTOR, PTEN, pPTEN, APOBEC3B) were assessed immunohistochemically and PIK3CA mutations (p.E542K, p.E545K, p.H1047R) by qPCR. Significantly more HPV16 positive tumors (89.29%) with low EGFR expression were found as compared to HPV negative ones (58.82%). PIK3CA mutations were detected in 7.14% of HPV16 positive and 2.5% of HPV negative cancers. In HPV16 positive patients survival analysis has shown that positive prognostic potential for disease free survival (DFS) had low expression of APOBEC3B. In HPV negative patients prognostic significance for DFS had APOBEC3B, Akt and pAkt(Thr308) levels, and for overall survival (OS) - pAkt(Thr308) only. Independent favorable prognostic factors in the whole group of patients were: low T stage, low pAkt(Thr308) expression, active HPV16 infection (for OS and DFS) and female gender (for OS). Obtained results suggest the existence of significant differences in expression and prognostic potential of proteins involved in EGFR/PI3K/Akt/mTOR signaling between HPV16 positive and HPV negative HNSCC patients.
本研究旨在比较 HPV16 阳性和 HPV 阴性头颈部鳞状细胞癌（HNSCC）患者中 PIK3CA 突变和参与或调节 EGFR/PI3K/Akt/mTOR 信号通路的蛋白表达的预后潜力。采用免疫组织化学法检测蛋白（EGFR、Akt、pAkt（Ser473）、pAkt（Thr308）、mTOR、PTEN、pPTEN、APOBEC3B）的表达，并通过 qPCR 检测 PIK3CA 突变（p.E542K、p.E545K、p.H1047R）。与 HPV 阴性肿瘤（58.82%）相比，HPV16 阳性肿瘤（89.29%）中发现更多低 EGFR 表达的肿瘤。在 HPV16 阳性肿瘤中检测到 7.14%的 PIK3CA 突变，而在 HPV 阴性肿瘤中检测到 2.5%的 PIK3CA 突变。在 HPV16 阳性患者的生存分析中，APOBEC3B 低表达对无病生存期（DFS）具有积极的预后潜力。在 HPV 阴性患者中，DFS 的预后意义与 APOBEC3B、Akt 和 pAkt（Thr308）水平相关，而 OS 仅与 pAkt（Thr308）相关。在所有患者中，独立的有利预后因素为：低 T 分期、低 pAkt（Thr308）表达、活跃的 HPV16 感染（OS 和 DFS）和女性性别（OS）。研究结果表明，HPV16 阳性和 HPV 阴性 HNSCC 患者中，参与 EGFR/PI3K/Akt/mTOR 信号通路的蛋白表达及其预后潜力存在显著差异。
