Role of ERM proteins and receptor-type tyrosine kinases in progression and metastasis of salivary gland carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K16921
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Kyushu University
• Principal Investigator: Hashimoto Kazuki 九州大学, 大学病院, 助教 (20707195)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 頭頸部腫瘍 / 唾液腺癌 / 浸潤転移 / 受容体型チロシンキナーゼ / 分子標的治療 / 免疫チェックポイント阻害剤

Outline of Final Research Achievements

1. High ezrin expression was detected in 28.5% patients with salivary gland carcinoma (SGC). Concomitant expression of ezrin and HER2 correlated significantly with shorter overall survival as well as a high incidence of distant metastasis. 2. Although EGFR overexpression and gene copy number gain were detected in 77.8% and 16.7% patients with recurrent and/or metastatic SGC respectively, the effectiveness of EGFR-targeted therapy was unremarkable. 3. PD-L1 expression (CPS≧1) was detected in 68.5% patients with recurrent and/or metastatic SGC, with a particularly high rate of expression in high-grade histological types such as salivary duct carcinoma (SDC) or poorly differentiated carcinoma. Although the efficacy of PD-1 inhibitor therapy in recurrent and/or metastatic SGC was limited, there is a potential therapeutic effect in SDC patients with high PD-L1 expression.

Free Research Field

頭頸部腫瘍

Academic Significance and Societal Importance of the Research Achievements

頭頸部に発生する悪性腫瘍のうち約90%は扁平上皮癌であり、唾液腺癌をはじめとした腺癌系統の組織型を主体とする非扁平上皮癌の発生は比較的まれである。しかしながらその病理組織型は非常に多彩であり、各々の組織型についての分子生物学的特性は十分には解明されておらず、転移再発例に対する有効なレジメンも存在しないのが現状である。本研究では、唾液腺癌各組織型の浸潤転移、予後における、ezrinやHER2、EGFRといった分子異常の関与を明らかにした。また、転移再発唾液腺癌症例に対する、HER2、EGFR、PD-1等を標的とした新規治療における効果予測因子の解明を行った。