人類端粒酶反轉錄酶於口腔鱗狀細胞癌與口腔癌前病變之表現

Abstract

背景: 端粒酶活性和人類端粒酶反轉錄酶訊息核醣核甘酸(hTERT mRNA)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hTERT蛋白質在82例口腔鱗狀細胞癌（OSCC），116例口腔上皮變異（OED），21例正常口腔黏膜（NOM）之表現。計算hTERT在OSCC、OED、和NOM細胞質和細胞核內的染色強度(SI)，染色指標(LIs，定義為在所有細胞中陽性染色細胞的百分比)和染色記分(LSs，定義為染色強度與染色指標的乘積)並比較組間差異。利用統計分析OSCCs細胞質或細胞核LSs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hTERT LSs從NOM (87±17%)， 經OED (95±18%) 至OSCC 樣本 (114±33%, P=0.000)，呈統計上有意義增加。平均細胞核hTERT LSs從NOM (80±14%)至OED (91±20%)也是增加，但至OSCC樣本(86±35%)則下降，三組間並無明顯統計上差異。平均細胞質hTERT LSs和OSCCs發生在男性(P=0.023)，較大的腫瘤體積 (T3和T4，P=0.048)，較高的臨床分期(第3和4期，P=0.033)，或患者有嚼食檳榔(P=0.029)，抽菸(P=0.027)和喝酒(P=0.025)等習慣有明顯相關。進一步看，OSCC患者若細胞核hTERT LSs高於100%，則復發率較高(P=0.044)，和五年存活率較低(P=0.011)。 結論: 我們的結果支持hTERT的過度表現在口腔癌形成早期即已發生，hTERT可作為OSCCs的生物指標。量測OSCC樣本細胞質或細胞核內hTERT的表現，也許可預測口腔癌的進程、復發和預後。

Background: Overexpression of telomerase activity or human telomerase reverse transcriptase (hTERT) mRNA has been demonstrated in a variety of human cancers and found to be associated with the tumor size, lymph node metastasis, clinical stage, recurrence, or prognosis of these cancers. Methods: In this study, we examined the expression of hTERT protein in 82 specimens of oral squamous cell carcinoma (OSCC), 116 specimens of oral epithelial dysplasia (OED), and 21 specimens of normal oral mucosa (NOM) by immunohistochemistry. The cytoplasmic and nuclear hTERT staining intensity (SI), labeling indices (LIs, defined as the percentage of positive cells in total cells), and labeling scores (LSs, defined as SI × LI) in OSCC, OED, and NOM samples were calculated and compared between groups. The correlation between the cytoplasmic or nuclear hTERT LS in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically. Results: The mean cytoplasmic hTERT LSs increased significantly from NOM (87±17%) through OED (95±18%) to OSCC samples (114±33%, P=0.000). The mean nuclear hTERT LSs also increased from NOM (80±14%) to OED (91±20%) and then decreased to OSCC samples (86±35%) with no statistically significant difference among the 3 groups. A significant correlation was found between the higher mean cytoplasmic hTERT LSs and OSCCs occurring in male patients (P=0.023), with larger tumor sizes (T3 and T4, P=0.048), with more advanced clinical stages (stages 3 and 4, P=0.033), or from patients with areca quid chewing (P=0.029), cigarette smoking (P=0.027), or alcohol drinking habits (P=0.025). In addition, OSCC patients with nuclear hTERT LSs greater than 100% were prone to have cancer recurrence (P=0.044) and a lower 5-year survival rate (P=0.011). Conclusion: Our results suggest that the increased expression of hTERT is an early event in oral carcinogenesis and hTERT may be a biomarker for OSCCs. Measuring the amount of cytoplasmic or nuclear expression of hTERT in OSCC samples may predict the oral cancer progression, recurrence, and prognosis.