探討缺氧誘導因子-1α表現與貓注射部位肉瘤之病理相關性

Abstract

缺氧是快速生長的實體瘤常見之微環境，這是由於異常的血管功能和快速的細胞分裂所致。在多種人類癌症中，已證實氧分子調控的轉錄因子缺氧誘導因子-1α (Hypoxia-inducible factor 1 alpha, HIF-1α) 過度表現，可於缺氧環境中調控細胞增殖、細胞凋亡、葡萄糖代謝、酸鹼值和血管新生。貓注射部位肉瘤 (Feline injection site sarcomas, FISSs) 是一群從注射部位之慢性炎症發展而來的軟組織肉瘤，臨床表現為快速生長的實體瘤，且往往由於手術不容易完全切除而導致復發。迄今，關於缺氧誘導因子-1α在貓注射部位肉瘤中的作用知之甚少。本研究的目的是檢測貓注射部位肉瘤中缺氧誘導因子-1α的表現，並評估其與貓注射部位肉瘤病理特徵的相關性。本研究樣本為90個選自西元2014年至2020年間診斷為原發性貓注射部位肉瘤的病例之福馬林固定石蠟包埋組織，以免疫組織化學染色偵測缺氧誘導因子-1α的表現。結果顯示，有61.1％的病例在細胞核內有缺氧誘導因子-1α的過度表現，統計分析結果顯示，過度表現缺氧誘導因子-1α與腫瘤分級和腫瘤壞死有顯著相關性，其中，有35.6％的病例被檢測出在壞死周圍有增強表現的缺氧誘導因子-1α，以上結果支持缺氧誘導因子-1α於促進貓注射部位肉瘤的生長上，可能發揮了重要的作用，並可作為一個潛在的治療靶位。

Hypoxia is a common microenvironment of rapidly-growing solid tumors owing to aberrant vascular function and rapid cell division. Overexpression of hypoxia-inducible factor 1 alpha (HIF-1α), the oxygen-regulated transcription factor, has been demonstrated in several human cancers and could upregulate cell proliferation, apoptosis, glucose metabolism, pH regulation, and angiogenesis, promoting tumor growth in a hypoxic condition. Feline injection-site sarcomas (FISSs), a group of soft-tissue sarcomas developing at the site of injection-induced chronic inflammation, are rapidly-growing solid tumors and clinically tend to recur due to incomplete excision. Little is known about the role of HIF-1α in FISS. The purpose of this study is to detect the expression of HIF-1α in FISSs and evaluate its correlation with the pathological features of FISS. Ninety formalin-fixed and paraffin-embedded specimens from cats diagnosed with primary FISS during 2014 to 2020 were selected. Immunohistochemistry staining for detecting HIF-1α expression was performed. Results showed that intranuclear overexpression of HIF-1α was detected in 61.1% of FISSs. The overexpression of HIF-1α was significantly associated with tumor grade and the presence of intra-tumoral necrosis. The peri-necrotic HIF-1α overexpression was detected in 35.6% of the HIF-1α-expressing FISSs. These results suggest that HIF-1α may play an important role on the promotion of FISSs and may serve as a potential therapeutic target.