Topoisomerase 2alpha plays a pivotal role in the tumor biology of stage IV thymic neoplasia.
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.
Liu
J M
JM
National Institute of Cancer Research, National Health Research Institutes (NICR, NHRI), Taipei, Taiwan, ROC.
Wang
L S
LS
Huang
M H
MH
Hsu
W H
WH
Yen
S H
SH
Shiau
C Y
CY
Li
A F Y
AF
Tiu
C M
CM
Tseng
S W
SW
Huang
B S
BS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000502:physiology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004250:DNA Topoisomerases, Type II / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015996:Survival Rate; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000532:radiotherapy
D000951:Antigens, Neoplasm; D002945:Cisplatin; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D005472:Fluorouracil; D002955:Leucovorin; D018719:Erb-b2 Receptor Tyrosine Kinases