在頭頸部鱗狀上皮癌中 T 和 Tn 抗原表現與癌病相關性

Abstract

細胞中蛋白質主要的兩種醣化修飾是N-linked glycoproteins 及 O-linked glycoprotein。Tn 抗原和T 抗原是O型糖化中修飾的前兩個醣基團。在許多癌症病人組織中，醣類抗原的表現會出現異常，導致組織中Tn 抗原和T 抗原的大量表現，發生的原因至今仍不明確。本次實驗取台大醫院的175個病人檢體，以凝集素針對Tn 抗原與T 抗原進行免疫組織染色，觀察在頭頸部鱗狀上皮癌切片中Tn 抗原與T 抗原的表現強度。以VVA偵測Tn表現量，結果顯示，相較於非腫瘤組織，71%的腫瘤組織，有較高的Tn 抗原表現量；以PNA偵測T表現量，結果顯示，相較於非腫瘤組織，69%的腫瘤組織，有較高的T 抗原表現量。之後統計抗原表現強度與各種病理診斷因子的臨床相關性。結果顯示，T 抗原在組織中表現量與淋巴血管浸潤(lymphovascular invasion,LVI)、淋巴結被膜外擴散(Extracapsular spread,ECS)、N stage及癌症分期(clinical stage)呈顯著相關(P<0.05)。腫瘤學上認為LVI、ECS、N stage是發生淋巴及遠端轉移的重要指標。目前對於上皮癌中T 抗原的表現在病理學上的影響仍不明確，未來仍需更多研究闡明T抗原的表現在頭頸部鱗狀上皮癌中對於轉移和癌症進程所扮演的角色。

N-linked glycoproteins and O-linked glycoproteins are two main glycoproteins in human cells. Tn and T antigens are the first two glycan units on O-linked glycan chain. Aberrant glycosylation is commonly found in tumors. Many studies have reported an increased Tn and T antigen expression is associated with tumor cell malignancy. However, the underlying mechanism resulting in altered Tn and T antigen expression in tumor malignancies are still poorly understood. In this study, we investigated the expression of the Tn and T antigens in 175 head and neck squamous cell carcinoma patients by immunohistochemistry staining with Vicia villosa agglutinin (VVA) lectin, specific for Tn antigen; and peanut agglutinin (PNA) lectin, specific for T antigen recognition. Our results indicate 71% of the patients display higher Tn antigen expression levels in the tumors compared with the corresponding non-tumor tissues; and 69% of the patients exhibit higher T antigen expression levels in the tumors compared with the corresponding non-tumor tissues. Furthermore, we examined whether Tn and T antigen expression levels correlate with HNSCC clinical pathophysiology. Patients identified with low T antigen expression levels were associated with lymphovascular invasion (LVI), extracapsular spread (ECS), and advanced N stage (P<0.05). LVI, ECS, and N stage are associated with metastasis to lymph nodes or distant sites and high risk of clinical progression. Currently, the implication of aberrant glycosylation and altered Tn and T antigen expressions in cancer malignancies remain unclear. Further studies on the regulation and functional significance of Tn and T antigen occurrence are still required in the understanding of HNSCC progression and metastasis.