Survivin於口腔鱗狀細胞癌之表現及其預後價值

Prognostic role of Survivin Expression in Oral Squamous Cell Carcinoma

吳大維(Ta-Wei Wu)

指導教授 ： 郭彥彬

國立臺灣大學/醫學院/臨床牙醫學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.00413

摘要

細胞凋亡對生物發育和維持正常生理活動非常重要。如果該凋亡的細胞沒有死亡，就可能導致細胞惡性增長，形成癌症。 在過去的幾年中，癌症的基礎研究集中在了解凋亡的異常，闡明致癌作用過程中這項重要的環節。 survivin 是最近被發現的一種細胞凋亡抑制蛋白。在膀胱癌、乳癌、腸癌、腦瘤、肺癌、淋巴癌等各類癌症中，有相當高程度的survivin表現，同時survivin的表現和癌症的預後有關。 由於survivin可以使得細胞逃過凋亡的訊號，便可不受控制地不斷繁殖，因此和癌症發生及抗藥性的產生有關。 本研究利用survivin抗體及免疫組織化學染色法，探討survivin於口腔鱗狀細胞癌中的表現及其預後價值。 survivin在口腔上皮變異及口腔鱗狀細胞癌中的陽性標記指數(Labeling index, LI)分別為36.3± 3.9% 及 53.7 ± 8.3%，且兩者有顯著之差異(P<0.001)。 在正常口腔頰黏膜則無survivin表現 。 在上皮變異部分，當survivin的染色率大於50%時，其之後較容易轉變為OSCC(P=0.0034) ，且此部分的陽性標記指數(Labeling index, LI)為47.0± 3.5%。 survivin的表現與腫瘤的大小(p = 0.0495)有顯著的相關。 Kaplan-Meier 存活分析發現survivin 標記指數大於50%的患者其整體存活率比起標記指數小於50%患者明顯為差(P =0.0145)。腫瘤較大的患者(T4)較腫瘤較小的患者(T1+T2+T3)其整體存活率明顯為差(P = 0.0019)。 臨床分期較高者(IV)較臨床分期較低者(I + II +III)其整體存活率也明顯為差(P =0.0343)。有復發之患者較無復發之患者其整體存活率也明顯為差 (P = 0.016)。低度與中度分化的腫瘤較分化高等者其整體存活率也明顯為差 (P =0.00639) 。 由於survivin陽性染色的表現與腫瘤的進行以及患者較差的預後有顯著的相關， 因此其表現可作為評估口腔癌預後有力的指標。 此外由於survivin在癌細胞中含量很豐富，但在正常細胞中卻幾乎不存在。 使得survivin可成為製造新抗癌藥物的標靶。

關鍵字

口腔鱗狀細胞癌 ； 細胞凋亡

並列摘要

Deregulated expression of inhibitors of apoptosis (programmed
cell death) may contribute to cancer by aberrantly extending cell
viability and facilitating the insurgence of resistance to therapy,
survivin has been implicated in the pathogenesis of several types of cancer. We have examined the expression of survivin in oral squamous cell carcinomas (SCCs) using anti- survivin antibody with an immunoperoxidase technique. Survivin cytoplasm staining was observed in 53 of the 87 (60.9%) cases of oral SCC. The mean labeling index of survivin-positive tumor cells was 53.7 ±8.3% (range 15~85%). When the expression of survivin in dysplasia was over 50%,it had higher potential to become SCC in the future (p=0.0034).The expression of Survivin was significantly correlated with increased tumor size (P = 0.0495), The Kaplan-Meier analysis showed that patients with tumors containing more than 50% survivin-positive cells had significantly shorter overall survival than those with tumors containing less than 50% survivin-positive cells (p=0.00145 by Log-rank & Wilcoxon tests). Patients with larger tumor size (T4) had significantly shorter overall survival than those with smaller tumor size (T1+T2+ T3) (p = 0.0019). Patients with advanced cancer stages(Stage IV) had significantly shorter overall survival than those with lower cancer stage (Stage I + Stage II +Stage III)(P =0.00343 by Cox-Mantel ). Patients with recurrence of cancer had significantly shorter overall survival than those without recurrence (P =0.016 by Cox-Mantel ). Patients with poorly and moderately differentiated cancers had significantly shorter overall survival than those with well-differentiated cancers (P = 0.00639 by Wilcoxon tests ). Patients with radiotherapy of cancer had significantly shorter overall survival than those without radiotherapy (P =0.047 by Cox-Mantel ). Patients with chemotherapy of cancer had significantly shorter overall survival than those without chemotherapy (P =0.0462 by Cox-Mantel ).
These data suggest that survivin expression may predictively identify cases of SCC with more aggressive and invasive clinical phenotype.Therefore, surviving can serve as a powerful prognostic factor of oral SCCs

並列關鍵字

survivin ； apoptosis ； SCC

參考文獻

王東堯：口腔檳榔癌.防癌雜誌,18: 26-27 1993

行政院衛生署：中華民國八十五年衛生統計.1996.台北

陳金勝，陳中和：口腔鱗狀細胞癌之統計分析報告.高雄醫學雜誌.11: 582-588 1995

鄭世榮,郭彥彬,江俊斌:CD44、CD44v基因產物於口腔鱗狀細胞癌之表現. 國立台灣大學臨床牙醫研究所口腔顎面外科組碩士文.1997

Adida, C., Berrebi, D., Peuchmaur, M., Reyes-Mugica, M., Altieri, DC . Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood 2000 ; 96 : 1921–1925.