HER-2 and TOP2A coamplification in urinary bladder cancer.
Standard
HER-2 and TOP2A coamplification in urinary bladder cancer. / Simon, Ronald; Atefy, Ramin; Wagner, Urs; Forster, Thomas; Fijan, André; Bruderer, James; Wilber, Kim; Mihatsch, Michael J; Gasser, Thomas; Sauter, Guido.
in: INT J CANCER, Jahrgang 107, Nr. 5, 5, 2003, S. 764-772.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - HER-2 and TOP2A coamplification in urinary bladder cancer.
AU - Simon, Ronald
AU - Atefy, Ramin
AU - Wagner, Urs
AU - Forster, Thomas
AU - Fijan, André
AU - Bruderer, James
AU - Wilber, Kim
AU - Mihatsch, Michael J
AU - Gasser, Thomas
AU - Sauter, Guido
PY - 2003
Y1 - 2003
N2 - HER-2/NEU is one of the most frequently amplified oncogenes and a potential therapeutic target in bladder cancer. In breast cancer, the adjacent TOP2A gene, the molecular target for several anticancer drugs, is frequently coamplified together with HER-2. To study the amplification and expression of TOP2A and HER-2 and associations with tumor phenotype and clinical outcome in bladder cancer, a tissue microarray containing 2,317 bladder tumor samples was analyzed by FISH and immunohistochemistry. Overall amplification frequencies were 6.3% for HER-2 and 1.5% for TOP2A. Amplifications were most frequently seen in advanced-stage (pT2-4) tumors (HER-2 13.8%, TOP2A 3.4%). Of HER-2-amplified tumors, 56% also had alterations of TOP2A, including 14.7% coamplifications, 33.3% gains and 8% deletions. Only 17.6% of TOP2A amplifications occurred independently of HER-2 alterations. Both HER-2 and TOP2A amplifications were significantly associated with advanced tumor stage (HER-2 p <0.0001, TOP2A p = 0.0218), high grade (p <0.0001 for both) and protein overexpression (p <0.0001 for both). TOP2A amplification and overexpression were linked to shortened survival in muscle-invasive tumors (p = 0.0042 and 0.0077, respectively). In summary, our data suggest that HER-2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer. The anatomy of the 17q12-q21 amplicon may be important for response to therapies targeting HER-2 or TOP2A.
AB - HER-2/NEU is one of the most frequently amplified oncogenes and a potential therapeutic target in bladder cancer. In breast cancer, the adjacent TOP2A gene, the molecular target for several anticancer drugs, is frequently coamplified together with HER-2. To study the amplification and expression of TOP2A and HER-2 and associations with tumor phenotype and clinical outcome in bladder cancer, a tissue microarray containing 2,317 bladder tumor samples was analyzed by FISH and immunohistochemistry. Overall amplification frequencies were 6.3% for HER-2 and 1.5% for TOP2A. Amplifications were most frequently seen in advanced-stage (pT2-4) tumors (HER-2 13.8%, TOP2A 3.4%). Of HER-2-amplified tumors, 56% also had alterations of TOP2A, including 14.7% coamplifications, 33.3% gains and 8% deletions. Only 17.6% of TOP2A amplifications occurred independently of HER-2 alterations. Both HER-2 and TOP2A amplifications were significantly associated with advanced tumor stage (HER-2 p <0.0001, TOP2A p = 0.0218), high grade (p <0.0001 for both) and protein overexpression (p <0.0001 for both). TOP2A amplification and overexpression were linked to shortened survival in muscle-invasive tumors (p = 0.0042 and 0.0077, respectively). In summary, our data suggest that HER-2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer. The anatomy of the 17q12-q21 amplicon may be important for response to therapies targeting HER-2 or TOP2A.
M3 - SCORING: Zeitschriftenaufsatz
VL - 107
SP - 764
EP - 772
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 5
M1 - 5
ER -
