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研究生:黃賢能
研究生(外文):Hsien-Neng Huang
論文名稱:卵巢透亮細胞癌之分子病理研究
論文名稱(外文):Molecular Genetic Alterations in Ovarian Clear Cell Carcinoma
指導教授:郭冠廷郭冠廷引用關係
指導教授(外文):Kuan-Ting Kuo
口試委員:鄭文芳林明杰
口試委員(外文):Wen-Fang ChengMing-Chieh Lin
口試日期:2015-07-22
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:病理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:61
中文關鍵詞:卵巢亮細胞癌ARID1APIK3CAZNF217TERT promoter預後
外文關鍵詞:ovarian clear cell carcinomaARID1APIK3CAZNF217TERT promoterprognosis
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AT-rich interactive domain 1A (ARID1A)是switch/sucrose non-fermentable (SWI/SNF)複合體的一個次單元。近年來,ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway,以及zinc finger protein 217 (ZNF217) gene被發現是常見於卵巢亮細胞癌的基因變化。E-cadherin表現以及telomerase reverse transcriptase (TERT) promoter突變也可以發生在部份的卵巢亮細胞癌。本研究的目的是找出這些分子基因變化的關連性,以及這些分子基因變化對於臨床預後以及治療的影響。我們發現ARID1A失去表現與年紀較輕、PI3K-Akt pathway變化、以及ZNF217 amplification有關。Chromosome 20q13.2 ZNF217 locus amplification與E-cadherin表現量下降相關。帶有activating PI3k-Akt pathway的卵巢亮細胞癌病人,E-cadherin表現量下降與FIGO stage晚期以及較短的overall survival相關。我們也發現對於早期卵巢亮細胞癌病人(FIGO stage I and II),TERT promoter突變與較短的disease-free survival和overall survival相關。若早期病人出現復發,帶有TERT promoter突變的病人,通常會於化療後六個月內復發。
我們的結果顯示:ARID1A失去表現與PI3K-Akt pathway活化以及ZNF217 amplification對於卵巢亮細胞癌形成可能有加成的效果。ZNF217可降低E-cadherin的表現,是未來可能的治療標的目標。對於帶有activating PI3K-Akt pathway的卵巢亮細胞癌病人,E-cadherin表現可做為預後因子。對於早期卵巢亮細胞癌的病人,TERT promoter突變是可能的治療標的。

AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose non-fermentable (SWI/SNF) complex. Recently, alterations of ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway and zinc finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma. E-cadherin and mutations of telomerase reverse transcriptase (TERT) promoter were found in some ovarian clear cell carcinomas. The present study was aimed at determining the correlation between these molecular events and other clinicopathological factors, including the prognostic impacts of these clinicopathological factors. We found that loss of ARID1A expression was significantly related to younger patient age, PI3K-Akt pathway activation and ZNF217 amplification. Chromosome 20q13.2 ZNF217 locus amplification was significantly associated with decreased E-cadherin expression. In ovarian clear cell carcinoma patients with activating PI3k-Akt pathway, decreased E-cadherin expression and advanced FIGO stage predicted shorter overall survival. We also found that in ovarian clear cell carcinoma patients with early FIGO stage (stage I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival. In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months.
Our results showed that synergic effects of loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma. ZNF217 plays a role in downregulating E-cadherin expression and is a potential therapeutic target for ovarian clear cell carcinoma patients. E-cadherin expression is a prognostic marker for ovarian clear cell carcinoma patients with activating PI3K-Akt pathway. In ovarian clear cell carcinoma of early FIGO stage, TERT promoter mutation is a potential therapeutic target.

口試委員會審定書 I I
中文摘要 II
英文摘要 IV
Contents VI
1. Introduction 1
1.1 Characteristics of ovarian clear cell carcinoma 1
1.2 ARID1A mutation and loss of ARID1A expression in ovarian clear cell carcinoma 1
1.3 PIK3CA mutation and ZNF217 amplification in ovarian clear cell carcinoma 2
1.4 Relationships of common genetic alterations in ovarian clear cell carcinoma 3
1.5 Relationships between E-cadherin expression and ZNF217 amplification 4
1.6 Telomerase reverse transcriptase (TERT) promoter mutation 5
2. Materials and Methods 7
2.1 Patients and tissue materials 7
2.2 Immunohistochemistry 7
2.3 DNA extraction and mutation analysis 8
2.4 Fluorescence in situ hybridization (FISH) 9
2.5 Statistical analysis 10
3. Results 11
3.1 Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma 11
3.2 Chromosome 20q13.2 ZNF217 locus amplification correlates with decreased E-cadherin expression in ovarian clear cell carcinoma with PI3K-Akt pathway alterations 12
3.3 TERT promoter mutation in ovarian clear cell carcinomas 14
4. Discussion 16
4.1 Loss of ARID1A and PI3K-Akt pathway activation as well as ZNF217 amplification may be related to the development of ovarian clear cell carcinoma 16
4.2 ZNF217 plays a role in downregulating E-cadherin expression and is a potential therapeutic target for ovarian clear cell carcinoma patients 20
4.3 E-cadherin expression is a prognostic marker for ovarian clear cell carcinoma patients with activating PI3K-Akt pathway 24
4.4 TERT promoter mutations were mutually exclusive with loss of ARID1A expression or PIK3CA mutations 25
4.5 In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow up during the initial 6 months following chemotherapy 26
5. Figures and Tables 28
Figure 1: Dual-color FISH chromosome 20q13.2 amplification 28
Figure 2: ARID1A, SMARCA2 and PTEN expressions 29
Figure 3: The correlation between PI3K-Akt pathway activation, ZNF217 amplification, and loss of ARID1A expression 30
Figure 4: Immunohistochemical stains of ZNF217 31
Figure 5: Kaplan–Meier curves of OS for the ovarian clear cell carcinoma patients classified by E-cadherin expression 32
Figure 6: Representative chromatograms of wild-type TERT promoter and mutational status of ovarian clear cell carcinomas 33
Figure 7: Relationship between disease-free/overall survival and TERT promoter mutation in patients with ovarian clear cell carcinoma 34
Figure 8: The relationships of molecular alterations of ovarian clear cell carcinoma in this study 36
Table 1: Manufacturers, clones, and dilution of antibodies 37
Table 2: Association between ARID1A expression and clinicopathological factors in ovarian clear cell carcinoma patients 38
Table 3: Univariate and multivariate analysis of survival in ovarian clear cell carcinoma patients 39
Table 4: Correlation of E-cadherin IHC and clinicopathological features 41
Table 5: Clinicopathological features in ovarian clear cell carcinoma patients with or without activating PI3K-Akt pathway 42
Table 6: Correlation of chromosome 20q13.2 amplification and clinicopathological features in ovarian clear cell carcinoma patients with or without activating PI3K-Akt pathway 43
Table 7: Univariate and multivariate analysis of risk factors for disease-free survival and overall survival in ovarian clear cell carcinoma patients 44
Table 8: Correlations between TERT promoter mutation and clinicopathological factors in ovarian clear cell carcinomas 47
Table 9: Univariate analysis of survival in ovarian clear cell carcinomas of all, early-stage and advanced-stage patients 48
6. Reference 51

1.Anglesio MS, Carey MS, Kobel M, Mackay H, Huntsman DG; Vancouver Ovarian Clear Cell Symposium Speakers. Clear cell carcinoma of the ovary: a report from the first Ovarian Clear Cell Symposium, June 24th, 2010. Gynecol Oncol 2011;121:407–415.
2.Pectasides D, Fountzilas G, Aravantinos G, et al. Advanced stage clear-cell epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol Oncol 2006;102:285–291.
3.Dallas PB, Pacchione S, Wilsker D, Bowrin V, Kobayashi R, Moran E. The human SWI-SNF complex protein p270 is an ARID family member with non-sequence-specific DNA binding activity. Mol Cell Biol 2000;20:3137–3146.
4.Phelan ML, Sif S, Narlikar GJ, Kingston RE. Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol Cell 1999;3:247–253.
5.Wiegand KC, Shah SP, Al-Agha OM, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 2010;363:1532–1543.
6.Fadare O, Renshaw IL, Liang SX. Does the Loss of ARID1A (BAF-250a) Expression in Endometrial Clear Cell Carcinomas Have Any Clinicopathologic Significance? A Pilot Assessment. J Cancer 2012;3:129–136.
7.Zhang X, Zhang Y, Yang Y, et al. Frequent low expression of chromatin remodeling gene ARID1A in breast cancer and its clinical significance. Cancer Epidemiol 2012;36:288–293.
8.Gui Y, Guo G, Huang Y, et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet 2011;43:875–878.
9.Wang DD, Chen YB, Pan K, et al. Decreased expression of the ARID1A gene is associated with poor prognosis in primary gastric cancer. PLoS One 2012;7:e40364.
10.Maeda D, Mao TL, Fukayama M, et al. Clinicopathological Significance of Loss of ARID1A Immunoreactivity in Ovarian Clear Cell Carcinoma. Int J Mol Sci 2010;11:5120–5128.
11.Kuo KT, Mao TL, Jones S, et al. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol 2009;174:1597–1601.
12.Kuo KT, Mao TL, Chen X, et al. DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma. Clin Cancer Res 2010;16:1997–2008.
13.Dobbin ZC, Landen CN. The Importance of the PI3K/AKT/MTOR Pathway in the Progression of Ovarian Cancer. Int J Mol Sci 2013;14:8213–8227.
14.Quinlan KG, Verger A, Yaswen P, Crossley M. Amplification of zinc finger gene 217 (ZNF217) and cancer: when good fingers go bad. Biochim Biophys Acta 2007;1775:333–340.
15.Collins C, Rommens JM, Kowbel D, et al. Positional cloning of ZNF217 and NABC1: Genes amplified at 20q13.2 and overexpressed in breast carcinoma. Proc Natl Acad Sci U S A 1998;95:8703-8.
16.Nonet GH, Stampfer MR, Chin K, Gray JW, Collins CC, Yaswen P. The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells. Cancer Res 2001;61:1250-4.
17.Hidaka S, Yasutake T, Takeshita H, et al. Differences in 20q13.2 copy number between colorectal cancers with and without liver metastasis. Clin Cancer Res 2000;6:2712-7.
18.Rahman MT, Nakayama K, Rahman M, et al. Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma. Cancer 2012;118:2846-57.
19.Hajra KM, Fearon ER. Cadherin and catenin alterations in human cancer. Genes Chromosomes Cancer 2002;34:255-68.
20.Howard S, Deroo T, Fujita Y, Itasaki N. A positive role of cadherin in wnt/beta-catenin signalling during epithelial-mesenchymal transition. PLoS One 2011;6:e23899.
21.He X, Chen Z, Jia M, Zhao X. Downregulated e-cadherin expression indicates worse prognosis in asian patients with colorectal cancer: Evidence from meta-analysis. PLoS One 2013;8:e70858.
22.Shi Y, Wu H, Zhang M, Ding L, Meng F, Fan X. Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol 2013;8:89,1596-8-89.
23.Quattrocchi L, Green AR, Martin S, Durrant L, Deen S. The cadherin switch in ovarian high-grade serous carcinoma is associated with disease progression. Virchows Arch 2011;459:21-9.
24.Ho CM, Cheng WF, Lin MC, et al. Prognostic and predictive values of E-cadherin for patients of ovarian clear cell adenocarcinoma. Int J Gynecol Cancer 2010;20:1490-7.
25.Cowger JJ, Zhao Q, Isovic M, Torchia J. Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: Identification of a ZNF217 consensus recognition sequence. Oncogene 2007;26:3378-86.
26.Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006;95 Suppl 1:S105–143.
27.Huang CY, Chen CA, Chen YL, et al. Nationwide surveillance in uterine cancer: survival analysis and the importance of birth cohort: 30-year population-based registry in Taiwan. PLoS One 2012;7:e51372.
28.Fadare O, Parkash V, Dupont WD, et al. The diagnosis of endometrial carcinomas with clear cells by gynecologic pathologists: an assessment of interobserver variability and associated morphologic features. Am J Surg Pathol 2012;36:1107–1118.
29.Gilks CB, Oliva E, Soslow RA. Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma. Am J Surg Pathol 2013;37:874–881.
30.Hoang LN, Han G, McConechy M, et al. Immunohistochemical characterization of prototypical endometrial clear cell carcinoma-diagnostic utility of HNF-1beta and oestrogen receptor. Histopathology 2014;64:585–596.
31.Fadare O, Renshaw IL, Liang SX. Does the Loss of ARID1A (BAF-250a) Expression in Endometrial Clear Cell Carcinomas Have Any Clinicopathologic Significance? A Pilot Assessment. J Cancer 2012;3:129–136.
32.Allo G, Bernardini MQ, Wu RC, et al. ARID1A loss correlates with mismatch repair deficiency and intact p53 expression in high-grade endometrial carcinomas. Mod Pathol 2014;27:255–261.
33.An HJ, Logani S, Isacson C, Ellenson LH. Molecular characterization of uterine clear cell carcinoma. Mod Pathol 2004;17:530–537.
34.Gunes C, Rudolph KL. The role of telomeres in stem cells and cancer. Cell 2013;152:390–393.
35.Harley CB. Telomerase and cancer therapeutics. Nat Rev Cancer 2008;8:167–179.
36.Widschwendter A, Muller HM, Hubalek MM, et al. Methylation status and expression of human telomerase reverse transcriptase in ovarian and cervical cancer. Gynecol Oncol 2004;93:407–416.
37.Horn S, Figl A, Rachakonda PS, et al. TERT promoter mutations in familial and sporadic melanoma. Science 2013;339:959–961.
38.Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science 2013;339:957–959.
39.Vinagre J, Almeida A, Populo H, et al. Frequency of TERT promoter mutations in human cancers. Nat Commun 2013;4:2185.
40.Landa I, Ganly I, Chan TA, et al. Frequent somatic TERT promoter mutations in thyroid cancer: higher prevalence in advanced forms of the disease. J Clin Endocrinol Metab 2013;98:E1562–1566.
41.Killela PJ, Reitman ZJ, Jiao Y, et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci U S A 2013;110:6021–6026.
42.Wu RC, Ayhan A, Maeda D, et al. Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynaecological malignancy. J Pathol 2014;232:473–481.
43.Lee KR, Tavassoli FA, Part J, et al. Surface epithelial-stromal tumours, In: Tavassoli FA, Devilee P (eds). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. IARC Press: Lyon; 2003. pp 117–145.
44.DeLair D, Oliva E, Kobel M, Macias A, Gilks CB, Soslow RA. Morphologic spectrum of immunohistochemically characterized clear cell carcinoma of the ovary: a study of 155 cases. Am J Surg Pathol 2011;35:36–44.
45.Kobel M, Kalloger SE, Carrick J, et al. A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary. Am J Surg Pathol 2009;33:14–21.
46.Maeda D, Shih I. Pathogenesis and the role of ARID1A mutation in endometriosis-related ovarian neoplasms. Adv Anat Pathol 2013;20:45–52.
47.Kurose K, Zhou XP, Araki T, Cannistra SA, Maher ER, Eng C. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am J Pathol 2001;158:2097–2106.
48.Kurose K, Zhou XP, Araki T, Cannistra SA, Maher ER, Eng C. Frequent loss of PTEN expression is linked to elevated phosphorylated akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am J Pathol 2001;158:2097-106.
49.Chan JK, Teoh D, Hu JM, Shin JY, Osann K, Kapp DS. Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers. Gynecol Oncol 2008;109:370–376.
50.Hashiguchi Y, Tsuda H, Inoue T, Berkowitz RS, Mok SC. PTEN expression in clear cell adenocarcinoma of the ovary. Gynecol Oncol 2006;101:71–75.
51.Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu Rev Biochem 2009;78:273–304.
52.Guan B, Wang TL, Shih I. ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. Cancer Res 2011;71:6718–6727.
53.Xiao W, Awadallah A, Xin W. Loss of ARID1A/BAF250a expression in ovarian endometriosis and clear cell carcinoma. Int J Clin Exp Pathol 2012;5:642–650.
54.Bosse T, Ter Haar NT, Seeber LM, et al. Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations, TP53 and microsatellite instability in endometrial cancer. Mod Pathol 2013 Epub May 24.
55.Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O. PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma. Virchows Arch 2012;460:77–87.
56.Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O. Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations. Mod Pathol 2012;25:615–624.
57.Nonet GH, Stampfer MR, Chin K, Gray JW, Collins CC, Yaswen P. The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells. Cancer Res 2001;61:1250–1254.
58.Huang G, Krig S, Kowbel D, et al. ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction. Hum Mol Genet 2005;14:3219–3225.
59.Krig SR, Miller JK, Frietze S, et al. ZNF217, a candidate breast cancer oncogene amplified at 20q13, regulates expression of the ErbB3 receptor tyrosine kinase in breast cancer cells. Oncogene 2010;29:5500–5510.
60.Rahman MT, Nakayama K, Rahman M, et al. Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma. Cancer 2012;118:2846–2857.
61.Cho H, Kim JS, Chung H, Perry C, Lee H, Kim JH. Loss of ARID1A/BAF250a expression is linked to tumor progression and adverse prognosis in cervical cancer. Hum Pathol 2013;44:1365–1374.
62.Katagiri A, Nakayama K, Rahman MT, et al. Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. Mod Pathol 2012;25:282–288.
63.Rahman M, Nakayama K, Rahman MT, et al. Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma. Hum Pathol 2012;43:2197–2206.
64.Ho CM, Lin MC, Huang SH, et al. PTEN promoter methylation and LOH of 10q22-23 locus in PTEN expression of ovarian clear cell adenocarcinomas. Gynecol Oncol 2009;112:307–313.
65.Shimizu T, Tolcher AW, Papadopoulos KP, et al. The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer. Clin Cancer Res 2012;18:2316–2325.
66.Goff BA, Sainz de la Cuesta R, Muntz HG, et al. Clear cell carcinoma of the ovary: A distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy in stage III disease. Gynecol Oncol 1996;60:412-7.
67.Sugiyama T, Kamura T, Kigawa J, et al. Clinical characteristics of clear cell carcinoma of the ovary: A distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer 2000;88:2584-9.
68.Wu RC, Ayhan A, Maeda D, et al. Frequent somatic mutations of the telomerase reverse transcriptase promoter in ovarian clear cell carcinoma but not in other major types of gynecologic malignancies. J Pathol 2014;232:473-81.
69.Quinlan KG, Verger A, Yaswen P, Crossley M. Amplification of zinc finger gene 217 (ZNF217) and cancer: When good fingers go bad. Biochim Biophys Acta 2007;1775:333-40.
70.Sarrio D, Moreno-Bueno G, Sanchez-Estevez C, et al. Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas. Hum Pathol 2006;37:1042-9.
71.Voutilainen KA, Anttila MA, Sillanpaa SM, et al. Prognostic significance of E-cadherin-catenin complex in epithelial ovarian cancer. J Clin Pathol 2006;59:460-7.
72.Rahman MT, Nakayama K, Rahman M, et al. Gene amplification of ZNF217 located at chr20q13.2 is associated with lymph node metastasis in ovarian clear cell carcinoma. Anticancer Res 2012;32:3091-5.
73.Watanabe T, Imoto I, Kosugi Y, et al. A novel amplification at 17q21-23 in ovarian cancer cell lines detected by comparative genomic hybridization. Gynecol Oncol 2001;81:172-7.
74.Gilks CB. Molecular abnormalities in ovarian cancer subtypes other than high-grade serous carcinoma. J Oncol 2010;2010:740968.
75.Janku F, Wheler JJ, Naing A, et al. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res 2013;73:276-84.
76.Hassan B, Akcakanat A, Holder AM, Meric-Bernstam F. Targeting the PI3-kinase/akt/mTOR signaling pathway. Surg Oncol Clin N Am 2013;22:641-64.
77.Littlepage LE, Adler AS, Kouros-Mehr H, et al. The transcription factor ZNF217 is a prognostic biomarker and therapeutic target during breast cancer progression. Cancer Discov 2012;2:638-51.
78.Howard EW, Camm KD, Wong YC, Wang XH. E-cadherin upregulation as a therapeutic goal in cancer treatment. Mini Rev Med Chem 2008;8:496-518.
79.Dobbin ZC, Landen CN. The importance of the PI3K/AKT/MTOR pathway in the progression of ovarian cancer. Int J Mol Sci 2013;14:8213-27.
80.Yamaguchi K, Mandai M, Toyokuni S, et al. Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res 2008;14:32–40.
81.Shin-Darlak CY, Skinner AM, Turker MS. A role for Pms2 in the prevention of tandem CC --> TT substitutions induced by ultraviolet radiation and oxidative stress. DNA Repair (Amst) 2005;4:51–57.
82.Liu T, Wang N, Cao J, et al. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene 2013, Epub ahead of print.
83.Wu S, Huang P, Li C, et al. Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study. Eur Urol 2014;65:274–277.
84.Melo M, da Rocha AG, Vinagre J, et al. TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas. J Clin Endocrinol Metab 2014;99:E754–765.
85.Morgan RJ,Jr, Alvarez RD, Armstrong DK, et al. Ovarian cancer, version 2.2013. J Natl Compr Canc Netw 2013;11:1199–1209.
86.Katagiri A, Nakayama K, Rahman MT, et al. Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. Mod Pathol 2012;25:282–288.
87.Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O. PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma. Virchows Arch 2012;460:77–87.
88.Ho CM, Lin MC, Huang SH, et al. PTEN promoter methylation and LOH of 10q22-23 locus in PTEN expression of ovarian clear cell adenocarcinomas. Gynecol Oncol 2009;112:307–313.
89.Abe A, Minaguchi T, Ochi H, et al. PIK3CA overexpression is a possible prognostic factor for favorable survival in ovarian clear cell carcinoma. Hum Pathol 2013;44:199–207.
90.Huang HN, Lin MC, Huang WC, Chiang YC, Kuo KT. Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma. Mod Pathol 2013, Epub ahead of print.
91.Maeda D, Mao TL, Fukayama M, et al. Clinicopathological Significance of Loss of ARID1A Immunoreactivity in Ovarian Clear Cell Carcinoma. Int J Mol Sci 2010;11:5120–5128.


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