鼻咽癌原發腫瘤體積與p53蛋白質之探討

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Title:	鼻咽癌原發腫瘤體積與p53蛋白質之探討 The primary tumor volume and p53 protein of nasopharyngeal carcinoma
Authors:	陳穆寬 Mu-Kuan Chen
Contributors:	中山醫學大學：醫學研究所;李鴻森;張正權
Keywords:	鼻咽癌;原發腫瘤體積;p53蛋白質 nasopharyngeal carcinoma;the primary tumor volume;p53 protein
Date:	2003
Issue Date:	2010-06-07T01:28:44Z (UTC)
Abstract:	研究背景：鼻咽癌為台灣的重要癌症之一，而目前對於鼻咽癌的治療是以放射線治療為主。在其他以放射線治療為主的癌症當中，原發腫瘤體積對其預後皆有重要的影響。然而，在預後較不好的原發腫瘤第三分期(T3)、原發腫瘤第四分期(T4)的鼻咽癌原發腫瘤體積和治療結果的關係卻還未有人深入研究。目前在頭頸部腫瘤最常見到的基因異常之一為p53，然而眾多研究的結果變異仍很大，在臨床上，是否可以應用為一種指標亦尚未明確。尤其是台灣在這個重要議題的研究上仍付之闕如。因此，以台灣的資料來進行本主題的研究確有其急迫性。目的：本論文之目的為 1. 研究在原發腫瘤第三分期(T3)、原發腫瘤第四分期(T4)內(within T3- and T4-staged)的鼻咽癌病人中，其原發腫瘤體積與治療結果的關聯，目的在於能否對TNM分期做更佳的修飾，並詳估治療方針是否需加以調整。 2. 研究鼻咽癌病人的原發腫瘤體積與P53蛋白質之間的關係。病人及方法：本研究從台灣某一家醫學中心收集鼻咽癌的新病例，以高解析度電腦斷層運用區域合成法(summation-of-area technique)精算原發腫瘤體積。p53蛋白質的呈現由免疫螢光染色測驗所得知。此研究的存活率分析是採用Kaplan及Meier之product-limit方法來估計，利用Log rank test來計算不同生存曲線之間的差異是否有統計學上有意義。統計分析採用Wilcoxon Rank Sums檢定及Fisher’s exact檢定，當P-value小於或等於0.05時，則被認定為是統計顯著。結果：經分析其資料結果顯示: (1) 在相同的原發腫瘤第T分期中可觀察原發腫瘤體積的大範圍變化。在原發腫瘤第T3分期之鼻咽癌腫瘤中，原發體積中位數為29.6ml，全距為8.0至131.8ml，較大的原發腫瘤體積明顯有較差的疾病存活率(P=0.0001) 。於原發腫瘤第T4分期的病人其原發腫瘤體積中位數為54.07ml，全距為6.7至223.1ml，較大的原發腫瘤明顯有較差的疾病存活率(P=0.0022)。(2) 若對p53染色有較強的正反應，其腫瘤體積愈大(P=0.03)，p53與臨床分期無關(P=0.84)。結論：在相同之原發腫瘤第三分期(T3)或原發腫瘤第四分期(T4)的鼻咽癌中，其原發腫瘤體積為重要的預後因子，若將原發腫瘤體積列入考慮，則可能使得AJCC分期系統更加詳盡。由於原發腫瘤體積和p53有正的相關性，因此，p53也許亦為一預後因子，原發腫瘤體積很大( > 60ml)的病人或有p53蛋白呈現時則應考慮更積極的治療。 Background: Nasopharyngeal carcinoma (NPC) is one of the leading causes of deaths in Taiwan. Tumor volume is an important prognostic factor in patients with malignancy treated with primary radiotherapy. As far as we know, the relationship between primary tumor volume and treatment outcome within the same T3- and T4-staged NPC (which has the worst prognosis), has not been studied. One of the most common genetic alternations in head and neck cancers is p53 abnormality, however, the results of published studies are highly variable, and the clinical application of this marker is still unclear. The relationship between primary tumor volume and p53 abnormality in NPC has never been studied. Therefore, this kind of study is urgent. Objectives: The aims of this thesis are: 1.To investigate the relationship between primary tumor volume and treatment outcome within T3- and T4-staged NPC, in order to better refine the TNM staging system and evaluate treatment strategy. 2. To clarify the relationship between primary tumor volume and p53 protein in NPC patients. Patients and Methods: Patients with newly diagnosed nasopharyngeal carcinoma and treated with high dose radiotherapy with or without chemotherapy were included in this study. Computed tomography-derived primary tumor volume was obtained following the summation of area technique. The p53 expression was evaluated from negative (-) to positive (+, ++, +++) by the immunohistochemistry stain. The probabilities of achieving tumor control and patient survival were estimated using the product-limit method of Kaplan and Meier and the log rank test was used for significance examination. The Wilcoxon Rank Sums test and Fisher’s exact test were used for statistical analysis. A P-value of 0.05 or less was considered to be statistically significant. Results: In T3-staged nasopharyngeal carcinoma, the median primary tumor volume was 29.6 ml, with a range of 8.0-131.8 ml. Large primary tumor volume was associated with a significantly poor disease-specific survival (P= 0.0001). In T4-staged cases, the median primary tumor volume was 54.07 ml, with a range of 6.7-223.1 ml. Larger primary tumor volume was also associated with a significantly poorer disease-specific survival (P= 0.0022 ). Patients with high p53 stains, the tumor volume was larger (p=0.03). p53 was found to be independent of clinical stage (p=0.84). Conclusion: Within the same T3- and T4-stage of nasopharyngeal carcinoma, the primary tumor volume represented an important prognostic factor. There is a positive correlation between the primary tumor volume and the p53 status. To improve the treatment outcome of nasopharyngeal carcinoma, T3- and T4-staged patients with large primary tumor volumes and patients with over-expression of p53 protein should be treated more promptly.
URI:	http://140.128.138.153:8080/handle/310902500/1608
Appears in Collections:	[醫學研究所] 博碩士論文

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