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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 臨床醫學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36955
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor鄭安理(Ann-Lii Cheng)
dc.contributor.authorChing-Hung Linen
dc.contributor.author林璟宏zh_TW
dc.date.accessioned2021-06-13T08:24:40Z-
dc.date.available2005-08-02
dc.date.copyright2005-08-02
dc.date.issued2005
dc.date.submitted2005-07-17
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36955-
dc.description.abstract背景
原發性中樞神經系統淋巴瘤(primary central nervous system lymphoma; PCNSL)是一個罕見的淋巴瘤,定義上須於診斷時只有中樞神經或腦膜受侵犯才可診斷為PCNSL。其病理組織型態,絕大多數被歸於瀰漫性大B細胞淋巴瘤(diffuse large B-cell lymphoma; DLBCL),這與一般源自週邊淋巴結(nodal lymphoma; NL)的瀰漫性大B細胞淋巴瘤在病理組織型態上並無法區分,然而這兩者的臨床表現及治療預後均有明顯的不同。過去PCNSL與NL的差異並未被直接比較過,本研究是以一組淋巴球分化標記來比較這兩者在表現率的差異,以及這些分化標記對於兩者預後的影響。
研究方法
我們首先收集台灣五個醫院包括台大醫院、奇美醫院、彰化基督教醫院、恩主公醫院及亞東醫院近10年來共52個PCNSL與72個NL病人的檢體及臨床資料。接著選取一組細胞分化標記來比較PCNSL與NL的差異。其中CD10與BCL-6是germinal center (GC)的標記,MUM-1是late GC/ early post GC的標記,vs38c與CD138是post GC的標記,所有標記在相同的條件下對所有的PCNSL與NL腫瘤進行免疫組織染色。以Chi- square及Fisher exact test分析這些標記在PCNSL與NL表現上之差異,並以Log-rank test及Cox proportional hazards model分析這些標記與PCNSL及NL預後的相關性。
結果
在所有51個PCNSL及72個NL檢體免疫組織染色結果顯示,細胞分化標記表現陽性的比率(PCNSL vs. NL)分別為CD10: 18% vs. 22% (P = 0.535); BCL-6: 61% vs. 46% (P = 0.156); MUM-1: 84% vs. 53% (P < 0.001); vs38c: 4% vs. 7% (P = 0.698); CD138: 0% vs. 0%; BCL-2: 49% vs. 51% (P = 0796)。MUM-1在PCNSL的表現比NL來的高,且於Bonferroni correction下仍達統計學上的意義。以分化程度區分,PCNSL比NL有較高的比率為Post-GC B-cell起源(P = 0.013; 78% vs. 62%)。分析29位以HD-MTX為第一線治療之PCNSL病人,單變項分析顯示BCL-6陽性有統計趨勢預後較佳(P = 0.073; median survival, 25.3 vs. 7.3 months),多變項分析顯示BCL-6為一獨立之預後因子。分析65位以CHOP或CHOP-like處方為第一線治療之NL病人,GCB次分類比non-GCB有較佳之預後(P = 0.003),於多變項分析顯示GCB為一獨立預後因子(P = 0.002)。
結論
我們的研究指出較多數的PCNSL被次分類為non-GCB,這主要是因為MUM-1在PCNSL的表現比NL來的高,由這些發現推測PCNSL可能源自比較成熟的細胞。對於PCNSL病人而言,BCL-6陽性的淋巴瘤可能有較佳的預後,而對於NL病人而言,GCB次分類有較佳之預後。
zh_TW
dc.description.abstractComparison of the Expression and Prognostic Significance of Differentiation Markers between Diffuse Large B-Cell Lymphoma of Central Nervous System Origin and Peripheral Nodal Origin
Purpose: Whether diffuse large B-cell lymphoma (DLBCL) of primary central nervous system origin (PCNSL) is biologically different from DLBCL of peripheral nodal origin (NL) remains unclear. The purpose of this study was to compare the expression frequency and prognostic significance of a panel of cell differentiation markers between these two disease entities.
Experimental design: This study included HIV-unrelated patients PCNSL (n=51) and NL (n=72) treated at four hospitals in Taiwan for whom archival tumor tissue was available. The lymphomas were morphologically subclassified according to updated Kiel classification criteria. Immunohistochemistry for CD10, BCL-6, MUM-1, vs38c, CD138 and BCL-2 was performed under the same conditions. The prognostic significance of clinical and immunophenotypic markers were evaluated in PCNSL patients that received HD-MTX based chemotherapy (n=29) and in NL patients that received CHOP or CHOP-like regimen (n=65) as first line treatment.
Results: The frequencies of expression (PCNSL vs. NL) for CD10, BCL-6, MUM-1, vs38c, CD138 and BCL-2 were 18% vs. 22% (P = 0.650), 61% vs. 46% (P = 0.200), 84% vs. 53% (P < 0.001), 4% vs. 7% (P = 0.698), 0% vs 0% and 49% vs 51% (P = 0.856) respectively. PCNSL tumors were more frequently classified as non -germinal center B cells (non-GCB) group than NL tumors (P = 0.020; 78% vs. 62%). In PCNSL, univariate analysis demonstrated that patients with BCL-6+ had a trend towards longer survival (P = 0.073; median survival, 25.3 vs. 7.3 months) and multivariate analysis confirmed expression of BCL-6 as an independent prognostic factor (P = 0.026). In NL, univariate and multivariate analyses demonstrated that GCB was significantly associated with longer survival.
Conclusion: Higher frequency of non-GCB classification in PCNSL implies that it has a more differentiated cellular origin than NL. Expression of BCL-6 is an important prognostic factor and its expression is more informative for prognosis in PCNSL than in NL.
en
dc.description.provenanceMade available in DSpace on 2021-06-13T08:24:40Z (GMT). No. of bitstreams: 1
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Previous issue date: 2005
en
dc.description.tableofcontents一.中文摘要 5
二.緒論 (Introduction) 7
PCNSL臨床簡介 7
PCNSL致病機轉與病理研究 7
PCNSL的治療 8
PCNSL的預後因子 9
本研究的假說 9
三. 研究材料及方法(Materials and Methods) 11
病人與檢體 11
組織型態分類 11
免疫組織染色及GCB/non-GCB次分類 11
統計分析 12
四. 結果 13
病人特色及治療 13
組織型態分類 13
免疫組織染色 13
存活及預後分析 13
五、討論 15
六.展望 17
七.英文摘要 18
八.參考文獻 19
九、表與圖 24
表一、PCNSL及NL病人的基本資料、治療與存活時間 24
表二、PCNSL及NL組織學次分類與GCB與non-GCB的關係 25
表三、PCNSL與NL抗原免疫染色的表現及GCB/non-GCB次分類 26
表四、單變項及多變項預後分析 27
圖一、B細胞分化過程與對應之分化標記 28
圖二、依免疫組織染色將DLBCL次分類為GCB與non-GCB 29
圖三、(A) Centroblast與Immunoblast型態示意圖。(B)PCNSL依細胞分類為CB之範例。 30
圖四、(A) PCNSL腫瘤BCL-6免疫染色陽性之範例。(B) PCNSL腫瘤MUM-1免疫染色陽性之範例。 31
圖五、(A) PCNSL病人依照BCL-6的表現與否分別的存活曲線圖。(B)NL病人GCB及non-GCB分類分別的存活曲線圖。 32
十、附錄 33
臨床試驗的理論基礎 33
臨床試驗設計 34
目的評估 34
病患篩選 34
統計考量 34
治療計劃 34
相關轉譯研究 (Correlative Translational Research) 35
dc.language.isozh-TW
dc.title原發性中樞神經系統淋巴瘤之研究zh_TW
dc.titleStudy of Primary Central Nervous System Lymphomaen
dc.typeThesis
dc.date.schoolyear93-2
dc.description.degree碩士
dc.contributor.oralexamcommittee田蕙芬(Hwei-Fang Tien),楊偉勛(Wei-Shiung Yang)
dc.subject.keyword中樞神經,淋巴瘤,zh_TW
dc.subject.keywordcentral nervous system,CNS,lymphoma,en
dc.relation.page35
dc.rights.note有償授權
dc.date.accepted2005-07-19
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept臨床醫學研究所zh_TW
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