國家衛生研究院 NHRI:Item 3990099045/11709

NHRI > National Institute of Cancer Research > Ming Jacqueline Liu(1996-2007) > Conference Papers/Meeting Abstract > Item 3990099045/11709

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Title:	Topoisomerase 2 alpha plays a pivotal role in the tumor biology of advanced thymic neoplasia
Authors:	Liu, JM;Hwang, BS;Wang, LS;Huang, MH;Yen, SH;Li, A;Tiu, CM;Whang-Peng, J
Contributors:	National Institute of Cancer Research
Abstract:	Background: Thymic carcinogenesis involves stepwise accumulation of genetic aberrations. Early tumors may experience loss at chromosome 6q25. Gains on chromosome 17q occur in about a third of thymic carcinomas, and is probably linked to amplification of the Topoisomerase 2α and Her-2/neu oncogenes. Patients and Methods: A treatment strategy had been developed for the management of stage IV thymic neoplasia since 1991, incorporating maximal surgical resection, combination chemotherapy using the CAP (cyclophosphamide 500mg/m2, adriamycin 50mg/m2, cisplatin0mg/m2) regimen, and radiation therapy potentiated by high dose weekly 5-fluorouracil leucovorin infusion. From 1991-2005, 35 stage IV(a+b) patients have been treated, including 18 females and 17 males, median age of 47years (range: 11 to 84). Histologically, 21 were thymic carcinoma, 13 type B3 and 1 type B2 thymoma. Selected tumor marker studies were performed retrospectively to correlate with chemotherapy responses in 29 patients with available specimen. Results: T2α gene amplification was identified in 4 aggressive thymic tumors, with concurrent amplification of the her2/neu gene in 3 patients. CAP chemotherapy was prescribed for 30 patients, with 3 complete and 18 partial responses, attaining a response rate of 70% (95% CI 52-84%), 37% experience grade 3+4 neutropenia with fever documented in 2 patients, but there were no mortalities. All responding patients over-expressed the T2α protein, whereas 4 non-responders had absence of protein expression (p=0.0002). Thymidylate synthase and ERCC1 expression was not correlated with tumor response to CAP therapy (p=1 and 0.543 respectively). In univariate analysis, factors significantly influencing patient survival included histological type (type B vs type C, p=0.0004), resectability (resectable vs unresectable, p=0.0009), Her2/neu gene amplification (negative vs positive, p=0.0284) Conclusions: Topoisomerase 2α gene amplification and protein over-expression plays a significant role in the tumor biology and therapy of thymic neoplasia. It is especially significant that expression of the topoisomerase 2α protein predicts chemotherapy response to an anthracycline containing regimen, and its absence predicts resistance.
Date:	2006-04
Relation:	Cancer Research. 2006 Apr;66(8, Suppl.):122-125.
Link to:	http://cancerres.aacrjournals.org/content/66/8_Supplement/125.4
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000454606201188
Appears in Collections:	[Ming Jacqueline Liu(1996-2007)] Conference Papers/Meeting Abstract [Jacqueline Whang-Peng(1996-2007)] Conference Papers/Meeting Abstract

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