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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡佳惠 | zh_TW |
dc.contributor.advisor | Jia-Huei Tsai | en |
dc.contributor.author | 林延儀 | zh_TW |
dc.contributor.author | Yen-Yi Lin | en |
dc.date.accessioned | 2023-09-18T16:07:50Z | - |
dc.date.available | 2023-11-10 | - |
dc.date.copyright | 2023-09-18 | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-07-13 | - |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/89717 | - |
dc.description.abstract | 微小乳突狀大腸直腸癌被認為是一種預後不良的大腸直腸癌,與淋巴血管和周圍神經侵犯呈現高度相關。微小乳突狀大腸直腸癌的定義為在所有腫瘤部位中至少有5%的微小乳突狀結構。組織學上,它由缺乏纖維血管性核心的微小乳突狀細胞團塊所構成且被緻密的纖維基質和空腔包圍。微小乳突狀細胞瘤因其細胞極性反轉呈現特殊的 “inside-out”結構。
在這項研究中,我們調查了2008年至2012年在國立台灣大學醫院切除的2148例大腸直腸癌樣本並診斷出49例微小乳突狀大腸直腸癌。並分析其臨床和病理特徵來進行研究。臨床特徵顯示微小乳突狀大腸直腸癌主要出現於男性並偏好於大腸左側。預後因子的分析中顯示微小乳突狀大腸直腸癌的分化較差且易出現高比例的腫瘤出芽和分化不良腫瘤團塊。腫瘤出芽和分化不良腫瘤團塊是目前新興的大腸直腸癌預後指標而且其與微小乳突狀大腸直腸癌的形態學相似。有趣的是,在多變量分析中,腫瘤出芽的比例比起分化不良腫瘤團塊的比例或診斷是否為微小乳突狀大腸直腸癌在預測病人預後上扮演著相對重要的角色。因此應優先考慮腫瘤出芽作為大腸直腸癌患者的預後指標。 之後我們利用標的次世代基因定序研究微小乳突狀大腸直腸癌提的分子特徵。經過驗證後我們發現TP53(10/12,92%)和APC(8/12,75%)突變率非常高,而KRAS(2/12,17%)突變率則較一般大腸直腸癌低。因此,我們進一步用免疫組織化學染色和桑格測序法去延伸次世代基因定序的結果。在我們研究群體中,微小乳突狀大腸直腸癌具有高比例p53的表現異常(47/49, 96%)、RAS / RAF熱點突變率低 (RAS: 10/49, 20%; RAF: 2/49, 4%)、及完全保留錯配修復蛋白染色(49/49, 100%)。綜合以上研究,微小乳突狀大腸直腸癌有著獨特的臨床病理及分子特色,不同於一般大腸直腸癌,可視為是獨特的型態學分類。 | zh_TW |
dc.description.abstract | Micropapillary colorectal carcinoma (MicCRC) is a subtype of colorectal cancer (CRC), characterized by poor prognosis, high lymphovascular, and perineural invasion. MicCRC is defined as having at least 5% of micropapillary structure in the tumor. Histologically, it is characterized by small papillary clusters of neoplastic cells that lack fibrovascular cores and are surrounded by dense fibrous stroma and lacunar spaces. Micropapillary carcinoma exhibits an “inside-out” pattern which shows reverse cell polarity. In this study, we investigated the clinical and pathological characteristics of 49 MicCRCs identified from 2128 resected CRC specimens at National Taiwan University Hospital from 2008 to 2012. Our results showed that MicCRC predominantly affects males and originates in the left side of the large intestine. It is associated with high-grade differentiation, tumor budding, and poorly differentiated clusters (PDCs). Tumor budding and PDCs share similar morphology with MicCRC and are new prognostic indicators in CRC, being associated with high tumor grade and advanced TNM stages. In multivariate analysis, tumor budding was found to play a critical role as a prognostic indicator in our cohort, rather than PDCs or diagnosis of MicCRC. Therefore, tumor budding should be given high priority as a prognostic indicator in CRC patients.
Our current understanding of the molecular pathways involved in MicCRC is still relatively preliminary. We submitted 12 MicCRCs to targeted next-generation sequencing to investigate the molecular features of MicCRC. The results demonstrated high mutation rates in TP53 (10/12 ,92%) and APC (8/12, 75%), low mutation rate in KRAS (2/12, 17%). Therefore, we utilized immunohistochemical and sanger sequencing to validate the results of NGS. We recognized that MicCRC exhibited high rate of aberrant p53 expression (47/49, 96%), preserved MMR expression (49/49, 100%), and low rate of RAS/RAF hotspot mutations (RAS: 10/49, 20%; BRAF: 2/49, 4%) in our cohort. These findings suggest that the molecular pathways involved in MicCRC differ from those in conventional CRC. | en |
dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-09-18T16:07:50Z No. of bitstreams: 0 | en |
dc.description.provenance | Made available in DSpace on 2023-09-18T16:07:50Z (GMT). No. of bitstreams: 0 | en |
dc.description.tableofcontents | 口試委員會審定書 I
摘要 II Abstract IV Contents VI 1. Introduction 1 2. Material and Methods 5 2.1 Tissue specimens. 5 2.2 Morphologic review. 5 2.3 Statistical analysis. 6 2.4 DNA extraction and targeted next-generation sequencing. 7 2.5 Validation by Sanger sequencing method. 8 2.6 Immunohistochemical validation. 9 3. Results 11 3.1 Morphology of MicCRC & prognosis factors 11 3.2 Clinical characteristic of MicCRC 11 3.3 Survival rates under different factors 13 3.4 Multivariate analysis 14 3.5 Targeted next-generation sequencing of MicCRC 15 3.6 Molecular features of MicCRC 16 4. Discussion 19 5. References 26 6. Figure 33 Figure 1. Morphology of MicCRC & prognosis factors 33 Figure 2. Comparison of clinicopathology features between CRCs and MicCRCs 36 Figure 3. Univariate survival analysis of different prognosis factors. 38 Figure 4. Overview of gene annotation of NGS (n=12) 39 Figure 5. Gene alteration of MicCRC (n=12) 41 Figure 6. Mutation mapper of mutated genes 42 Figure 7. IHC results of MicCRC. 43 7. Table 45 Table 1. Clinicopathological features of MicCRC. 45 Table 2. Correlation between clinicopathological between MicCRC and CRC. 46 Table 3. Survival analysis of MicCRC. 47 Table 4. Molecular features of MicCRC 48 Table 5. RAS/RAF mutation in MicCRC 49 8. Supplementary table 50 Supplementary table 1. Targeting genes included in QIAseq Comprehensive Cancer Panel 50 Supplementary table 2. Sanger sequencing primer 52 Supplementary table 3. Variants details of the mutated genes. 53 Supplementary table 4. Variants details of the uncertain genes. 56 | - |
dc.language.iso | en | - |
dc.title | 微小乳突狀大腸直腸癌的臨床病理及分子特徵 | zh_TW |
dc.title | The clinicopathological and molecular features of micropapillary colorectal carcinoma | en |
dc.type | Thesis | - |
dc.date.schoolyear | 111-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 鄭永銘;林本仁 | zh_TW |
dc.contributor.oralexamcommittee | Yung-Ming Jen;Been-Ren Lin | en |
dc.subject.keyword | 微小乳突狀癌,大腸直腸癌,腫瘤出芽,分化不良腫瘤團塊,TP53,RAS/RAF, | zh_TW |
dc.subject.keyword | micropapillary carcinoma,colorectal carcinoma,tumor budding,poorly differentiated clusters,TP53,RAS/RAF, | en |
dc.relation.page | 59 | - |
dc.identifier.doi | 10.6342/NTU202301505 | - |
dc.rights.note | 同意授權(全球公開) | - |
dc.date.accepted | 2023-07-14 | - |
dc.contributor.author-college | 醫學院 | - |
dc.contributor.author-dept | 病理學研究所 | - |
顯示於系所單位: | 病理學科所 |
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