Topoisomerase 2α plays a pivotal role in the tumor biology of stage IV thymic neoplasia

J. M. Liu, L. S. Wang, M. H. Huang, W. H. Hsu, S. H. Yen, C. Y. Shiau, A. F Y Li, C. M. Tiu, S. W. Tseng, B. S. Huang

Research output: Contribution to journalArticle

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Abstract

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 2α (T2α) 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. T2α 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 (≥10% nuclei positive) the T2α protein, whereas 4 non-responders had very low expression. T2α 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. T2α and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.

Original languageEnglish
Pages (from-to)502-509
Number of pages8
JournalCancer
Volume109
Issue number3
DOIs
Publication statusPublished - Feb 1 2007
Externally publishedYes

Fingerprint

Thymoma
Doxorubicin
Cyclophosphamide
Cisplatin
Neoplasms
Gene Amplification
Survival
erbB-2 Genes
Familial Thymoma
Combination Drug Therapy
Fluorouracil
Microsatellite Repeats
Histology
Radiotherapy
Chromosomes
Confidence Intervals
Therapeutics
Genes
Proteins

Keywords

  • Anthracyclines
  • Her-2/neu
  • Thymic carcinoma
  • Topoisomerase 2α

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Liu, J. M., Wang, L. S., Huang, M. H., Hsu, W. H., Yen, S. H., Shiau, C. Y., ... Huang, B. S. (2007). Topoisomerase 2α plays a pivotal role in the tumor biology of stage IV thymic neoplasia. Cancer, 109(3), 502-509. https://doi.org/10.1002/cncr.22404

Topoisomerase 2α plays a pivotal role in the tumor biology of stage IV thymic neoplasia. / Liu, J. M.; Wang, L. S.; Huang, M. H.; Hsu, W. H.; Yen, S. H.; Shiau, C. Y.; Li, A. F Y; Tiu, C. M.; Tseng, S. W.; Huang, B. S.

In: Cancer, Vol. 109, No. 3, 01.02.2007, p. 502-509.

Research output: Contribution to journalArticle

Liu, JM, Wang, LS, Huang, MH, Hsu, WH, Yen, SH, Shiau, CY, Li, AFY, Tiu, CM, Tseng, SW & Huang, BS 2007, 'Topoisomerase 2α plays a pivotal role in the tumor biology of stage IV thymic neoplasia', Cancer, vol. 109, no. 3, pp. 502-509. https://doi.org/10.1002/cncr.22404
Liu JM, Wang LS, Huang MH, Hsu WH, Yen SH, Shiau CY et al. Topoisomerase 2α plays a pivotal role in the tumor biology of stage IV thymic neoplasia. Cancer. 2007 Feb 1;109(3):502-509. https://doi.org/10.1002/cncr.22404
Liu, J. M. ; Wang, L. S. ; Huang, M. H. ; Hsu, W. H. ; Yen, S. H. ; Shiau, C. Y. ; Li, A. F Y ; Tiu, C. M. ; Tseng, S. W. ; Huang, B. S. / Topoisomerase 2α plays a pivotal role in the tumor biology of stage IV thymic neoplasia. In: Cancer. 2007 ; Vol. 109, No. 3. pp. 502-509.
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abstract = "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 2α (T2α) 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. T2α 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 (≥10{\%} nuclei positive) the T2α protein, whereas 4 non-responders had very low expression. T2α 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. T2α and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.",
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AU - Hsu, W. H.

AU - Yen, S. H.

AU - Shiau, C. Y.

AU - Li, A. F Y

AU - Tiu, C. M.

AU - Tseng, S. W.

AU - Huang, B. S.

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N2 - 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 2α (T2α) 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. T2α 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 (≥10% nuclei positive) the T2α protein, whereas 4 non-responders had very low expression. T2α 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. T2α and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.

AB - 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 2α (T2α) 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. T2α 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 (≥10% nuclei positive) the T2α protein, whereas 4 non-responders had very low expression. T2α 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. T2α and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.

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