細胞凋亡抑制蛋白1於口腔鱗狀細胞癌與口腔癌前病變之表現

Abstract

背景: 細胞凋亡抑制蛋白1 (cIAP-1)的過度表現，已經在不同的人類癌症中被發現，且和腫瘤的大小，淋巴結的轉移，腫瘤分期，復發和預後等有關。 方法: 在本研究中，我們利用免疫組織化學染色法，探討cIAP-1蛋白質在73例口腔鱗狀細胞癌（OSCC），76例口腔上皮變異（OED；23例輕度，34例中度，19例重度上皮變異），31例正常口腔黏膜（NOM）之表現。計算cIAP-1在OSCC、OED、和NOM細胞質的染色強度(staining intensity, SI)和染色指標(labeling indices, LIs，定義為在所有細胞中陽性染色細胞的百分比)並比較組間差異。利用統計分析OSCCs細胞質LIs和臨床參數或存活率間的關連性。 結果: 結果顯示平均細胞質cIAP-1 LIs從NOM (23±22%)， 經OED (50±25%) 至OSCC 樣本 (73±17%)，呈統計上有意義增加 (NOM v.s. OED or OSCC, P=0.000; OED v.s. OSCC, P=0.000)。平均細胞質cIAP-1 LIs和OSCCs和局部淋巴轉移(P=0.000)，和較高的臨床分期(P=0.045)有明顯相關。 結論: 我們的結果顯示，cIAP-1廣泛地表現在正常的、變異的與惡性的口腔上皮細胞之細胞質中。而cIAP-1在細胞質的表現從NOM至OED至OSCC有顯著的增加。量測OSCC樣本細胞質cIAP-1的表現，也許可預測口腔癌的進程、復發和預後。 關鍵字: 細胞凋亡抑制蛋白1，口腔癌，口腔癌前病變

Background: Overexpression of cellular inhibitor of apoptosis protein 1 (cIAP-1) has been demonstrated in a variety of human cancers and found to be associated with the lymph node metastasis, clinical stage, recurrence, or prognosis of these cancers. Methods: In this study, we examined the expression of cIAP-1 protein in 73 specimens of oral squamous cell carcinoma (OSCC), 76 specimens of oral epithelial dysplasia (OED), and 31 specimens of normal oral mucosa (NOM) by immunohistochemistry. The cytoplasmic cIAP-1 labeling indices (LIs) in OSCC, OED, and NOM samples were calculated and compared between groups. The correlation between the cytoplasmic cIAP-1 LI in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically. Results: The mean cytoplasmic cIAP-1 LIs increased significantly from NOM (23 ± 22%) through OED (50 ± 25%) to OSCC samples (73 ± 17%) (P = 0.000). A significant correlation was found between the higher mean cytoplasmic cIAP-1 LIs and OSCCs with positive lymph node metastasis (P = 0.000) or more advanced clinical stages (P=0.045). Conclusion: Our results suggest that the increased expression of cIAP-1 is an early event in oral carcinogenesis and the cIAP-1 may be a biomarker for OSCCs. Measuring the amount of cytoplasmic cIAP-1 expression in OSCC samples may predict the oral cancer progression in Taiwan. Key words: cellular inhibitor of apoptosis protein 1, oral cancer, oral precancer