Topoisomerase 2alpha plays a pivotal role in the tumor biology of stage IV thymic neoplasia. 2007

J M Liu, and L S Wang, and M H Huang, and W H Hsu, and S H Yen, and C Y Shiau, and A F Y Li, and C M Tiu, and S W Tseng, and B S Huang
National Institute of Cancer Research, National Health Research Institutes (NICR, NHRI), Taipei, Taiwan, ROC.

BACKGROUND Microsatellite studies in histologic types B3 and C thymic neoplasia detected gains on chromosome 17q, which contains the Her-2/neu and its juxtaposed topoisomerase 2alpha (T2alpha) genes. The study aimed to evaluate their impact on tumor biology and survival of advanced thymic neoplasia patients. METHODS From 1991 to 2005, 36 consecutive stage IV thymic carcinoma patients were treated, 18 men and 18 women, aged 11 to 84 years. There were 22 thymic carcinoma, 13 type B3, and 1 type B2 thymoma. Patients received treatment consisting of surgical resection, combination chemotherapy with the CAP (cyclophosphamide, Adriamycin, cisplatin) regimen, or radiation therapy potentiated by high-dose weekly 5-fluorouracil infusion. Permutations of these 3 treatment modalities were prescribed as necessary. RESULTS T2alpha gene amplification was detected in 4 of 14 thymic carcinoma and 1 of 15 type B3 thymoma. Three thymic carcinoma patients had Her-2/neu coamplification and these 3 patients had rapidly growing tumor and extensive disease at initial diagnosis. CAP was prescribed in 28 patients and 20 patients responded (response rate, 71.4%, 95% confidence interval [CI]: 52.8% to 85%); all responders overexpressed (> or = 10% nuclei positive) the T2alpha protein, whereas 4 nonresponders had very low expression. T2alpha overexpression predicts CAP response, and its absence predicts resistance (P = .001). Overall survival was significantly prolonged if the tumor was resectable (P = .001), of type B3 histology (P = .0039), and had no Her-2 gene amplification (P = .0081). CONCLUSIONS T2alpha and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.

UI MeSH Term Description Entries
D007124 Immunoenzyme Techniques Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens. Antibody Enzyme Technique, Unlabeled,Enzyme Immunoassay,Enzyme-Labeled Antibody Technique,Immunoassay, Enzyme,Immunoperoxidase Techniques,Peroxidase-Antiperoxidase Complex Technique,Peroxidase-Labeled Antibody Technique,Antibody Enzyme Technic, Unlabeled,Enzyme-Labeled Antibody Technic,Immunoenzyme Technics,Immunoperoxidase Technics,Peroxidase-Antiperoxidase Complex Technic,Peroxidase-Labeled Antibody Technic,Antibody Technic, Enzyme-Labeled,Antibody Technic, Peroxidase-Labeled,Antibody Technics, Enzyme-Labeled,Antibody Technics, Peroxidase-Labeled,Antibody Technique, Enzyme-Labeled,Antibody Technique, Peroxidase-Labeled,Antibody Techniques, Enzyme-Labeled,Antibody Techniques, Peroxidase-Labeled,Enzyme Immunoassays,Enzyme Labeled Antibody Technic,Enzyme Labeled Antibody Technique,Enzyme-Labeled Antibody Technics,Enzyme-Labeled Antibody Techniques,Immunoassays, Enzyme,Immunoenzyme Technic,Immunoenzyme Technique,Immunoperoxidase Technic,Immunoperoxidase Technique,Peroxidase Antiperoxidase Complex Technic,Peroxidase Antiperoxidase Complex Technique,Peroxidase Labeled Antibody Technic,Peroxidase Labeled Antibody Technique,Peroxidase-Antiperoxidase Complex Technics,Peroxidase-Antiperoxidase Complex Techniques,Peroxidase-Labeled Antibody Technics,Peroxidase-Labeled Antibody Techniques,Technic, Enzyme-Labeled Antibody,Technic, Immunoenzyme,Technic, Immunoperoxidase,Technic, Peroxidase-Antiperoxidase Complex,Technic, Peroxidase-Labeled Antibody,Technics, Enzyme-Labeled Antibody,Technics, Immunoenzyme,Technics, Immunoperoxidase,Technics, Peroxidase-Antiperoxidase Complex,Technics, Peroxidase-Labeled Antibody,Technique, Enzyme-Labeled Antibody,Technique, Immunoenzyme,Technique, Immunoperoxidase,Technique, Peroxidase-Antiperoxidase Complex,Technique, Peroxidase-Labeled Antibody,Techniques, Enzyme-Labeled Antibody,Techniques, Immunoenzyme,Techniques, Immunoperoxidase,Techniques, Peroxidase-Antiperoxidase Complex,Techniques, Peroxidase-Labeled Antibody
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009367 Neoplasm Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002886 Chromosomes, Human, Pair 17 A specific pair of GROUP E CHROMOSOMES of the human chromosome classification. Chromosome 17
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D002955 Leucovorin The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS. Calcium Leucovorin,Citrovorum Factor,Folinic Acid,N(5)-Formyltetrahydrofolate,5-Formyltetrahydrofolate,5-Formyltetrahydropteroylglutamate,Calcium Folinate,Folinic Acid-SF,Leucovorin, (D)-Isomer,Leucovorin, (DL)-Isomer,Leucovorin, (R)-Isomer,Leucovorin, Calcium (1:1) Salt,Leucovorin, Calcium (1:1) Salt, (DL)-Isomer,Leucovorin, Calcium (1:1) Salt, Pentahydrate,Leucovorin, Monosodium Salt,Leukovorin,Leukovorum,Wellcovorin,5 Formyltetrahydrofolate,5 Formyltetrahydropteroylglutamate,Acid, Folinic,Factor, Citrovorum,Folinate, Calcium,Folinic Acid SF,Leucovorin, Calcium,Monosodium Salt Leucovorin
D003131 Combined Modality Therapy The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used. Multimodal Treatment,Therapy, Combined Modality,Combined Modality Therapies,Modality Therapies, Combined,Modality Therapy, Combined,Multimodal Treatments,Therapies, Combined Modality,Treatment, Multimodal,Treatments, Multimodal
D003520 Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. (+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271

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