探討p53和酥胺基酸705磷酸化的Stat3（Signal Transducer and Activator of Transcription 3）在南台灣頭頸部鱗狀細胞癌中的表現和彼此的相關性

The Expression and Association of p53 and p- Stat3（Tyr705） in Head and Neck Squamous Cell Carcinoma in Southern Taiwan

胡士文(Shih-Wen Hu)

指導教授 ： 蔡志仁

高雄醫學大學/醫學院/醫學研究所/碩士(2006年)

摘要

目的：p53腫瘤抑制基因的突變和p-Stat3 (Tyr705)（signal transducer and activator of transcription 3）致癌基因的組織活化，在很多癌症上都可觀察到。有關Stat3 (Tyr705)磷酸化和p53在頭頸部腫瘤的研究很多，但是沒有真正同時含蓋口咽部、咽下部、喉部的頭頸部鱗狀上皮細胞癌，以及目前對於南台灣嚼檳榔族群的頭頸部鱗狀上皮細胞癌中，Stat3 (Tyr705)磷酸化的組織活化表現以及p53與Stat3 (Tyr705)磷酸化之間是否有調控關係，這部份仍舊不太了解，我們試著找出p-Stat3 (Tyr705)是否跟細胞組織中p53高度表現，彼此間有功能性的調節作用關係存在。據我們所知這是第一篇研究南台灣嚼檳榔族群真正同時含蓋口咽部、咽下部、喉部的頭頸部鱗狀上皮細胞癌的樣本研究，並且研究Stat3 (Tyr705)磷酸化在頭頸部鱗狀上皮細胞癌中的表現，以及p53與Stat3 (Tyr705)磷酸化之間是否有調控關係。
材料及方法：蒐集西元1990到2002年間南台灣高雄醫學大學附設醫院頭頸部鱗狀上皮細胞癌的病患87名，追蹤病患從癌症病理診斷起到西元2005年12底止，病患資料來源來自病歷記載，扣除追蹤期間失去追蹤和資料不全病患，剩餘的案例有66例，含口咽部鱗狀上皮細胞癌10例、咽下部鱗狀上皮細胞癌17例、喉部的鱗狀上皮細胞癌39例，收集石蠟包埋的標本進行p53與p-Stat3 (Tyr705)的免疫染色，觀察它們免疫組織化學染色的位置和表現量，以半定量的方式記錄其表現量，之後進行統計分析，p值小於0.05則認為有統計意義。
結果：頭頸部鱗狀上皮細胞癌的整體p53免疫組織化學染色表現非常接近有顯著統計學上的差異（p=0.051），而p-Stat3 (Tyr705)免疫組織化學染色的組織活化現象，達到顯著統計學上的差異（p=0.009）。檳榔與p53、p-Stat3 (Tyr705)的表現無關（分別是p=0.700和p=1.000），抽煙與p53、p-Stat3 (Tyr705)的表現無關（分別是p=0.611和p=0.723），喝酒與p53、p-Stat3 (Tyr705)的表現無關（分別是p=0.128和p=0.783），臨床變數如年齡和腫瘤分期T分期也跟p53、p-Stat3 (Tyr705)的表現無關（分別是p=0.362、p=0.375、p=1.000和p=0.601），p53和p-Stat3 (Tyr705)之間，可能有調控關係存在（p=0.087）。
結論：p-Stat3 (Tyr705)的活化與頭頸部鱗狀上皮細胞癌的生長有關，p53在頭頸部鱗狀上皮細胞癌似乎有過度表現的趨勢，p-Stat3 (Tyr705)對於頭頸部鱗狀上皮細胞癌的病理機轉，扮演著重要角色，p53似乎對於頭頸部鱗狀上皮細胞癌的腫瘤產生機轉，也扮演著重要角色，而嚼檳榔不管有無抽菸，可能都不經由p53或p-Stat3 (Tyr705)的病理途徑，而p53和p-Stat3 (Tyr705)之間似乎跟乳癌相同，也有彼此的調控關係存在。

關鍵字

免疫組織化學染色 ； 頭頸部 ； 鱗狀上皮細胞癌 ； p53 ； 酥胺基酸705磷酸化的Stat3

並列摘要

Purpose: The mutation of p53 tumor suppressor gene and constitutive activation of oncogene Stat3（signal transducer and activator of transcription 3）can be observed in many tumors. There were lots of papers concerning p53 and Stat3 in head and neck tumors. However it’s not clear that the role of phosphorylated Stat3 or the modulation of Stat3 by p53 in betel-related head and neck squamous cell carcinoma in southern Taiwan. We try to find out if there exists the functional modulation of p-Stat3 (Tyr705) by p53 overexpression. To the best of our knowledge, this is the first paper concerning the p-Stat3 in betel-related head and neck squamous cell carcinoma, including oropharyngeal, hypopharyngeal, and laryngeal carcinoma, as well as the functional relationship of p53 overexpression and p- Stat3 in southern Taiwan.
Materials and methods: Eighty-seven patients diagnosed as having primary head and neck squamous cell carcinoma were retrieved from Kaohsiung Medical University Chung-Ho Memorial Hospital between 1990 and 2002, prior to treatment. We follow up these patients until December 2005. Clinical files were all retrieved from medical records. Twenty-one patients were abandoned due to inadequate clinical data and/or lose follow up. Only sixty-six patients, including ten oropharyngeal squamous cell carcinoma, seventeen hypopharyngeal squamous cell carcinoma, and thirty-nine laryngeal squamous cell carcinoma, recruited for the study were chosen consecutively and immunohistochemical analysis was done for the cases. Paraffin embedded tissue blocks were used for immunostaining of p53 and p-Stat3 (Tyr705). Then we record the location and semi-quantitative measurement of immunostaining results.
Results: Compared with normal epithelium, the overexpression of p53 in head and neck tumors is statistically marginal significant (p=0.051). The constitutive activation of p-Stat3 (Tyr705) is statistically significant (p=0.009). The overexpression of p53 and constitutive activation of p-Stat3 (Tyr705) are not related to betel quid-chewing, smoking, and alcohol (p=0.700, p=1.000, p=0.611, p=0.723, p=0.128, and p=0.783 respectively）. The clinical parameters such as age and T stage are also unrelated to pathogenesis of p53 and p-Stat3 (Tyr705)（p=0.362, p=0.375, p=1.000, and p=0.601 respectively）. The functional modulation of p-Stat3 (Tyr705) by p53 is marginal statistically significant in our study（p=0.087）.
Conclusions: The constitutive activation of p-Stat3 (Tyr705) contributes to the growth of head and neck squamous cell carcinoma. The overexpression of p53 seems to exist in head and neck squamous cell carcinoma. Both p53 and p-Stat3 (Tyr705) may contribute to the pathogenesis of head and neck squamous cell carcinoma. Betel quid-chewing with or without smoking is probably not involved in the carcinogenesis of head and neck squamous cell carcinoma. There is marginally significant modulation of p-Stat3 (Tyr705) by p53 in our study, which may be consistent with the previous study.

並列關鍵字

immunohistochemical staining ； head and neck ； squamous cell carcinoma ； p53 ； p-Stat3 (Tyr705)

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