Prognostic relevance of gene amplifications and coamplifications in breast cancer.
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Prognostic relevance of gene amplifications and coamplifications in breast cancer. / Al-Kuraya, Khawla; Schraml, Peter; Torhorst, Joachim; Tapia, Coya; Zaharieva, Boriana; Novotny, Hedvika; Spichtin, Hanspeter; Maurer, Robert; Mirlacher, Martina; Köchli, Ossi; Zuber, Markus; Dieterich, Holger; Mross, Friedrich; Wilber, Kim; Simon, Ronald; Sauter, Guido.
In: CANCER RES, Vol. 64, No. 23, 23, 2004, p. 8534-8540.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Prognostic relevance of gene amplifications and coamplifications in breast cancer.
AU - Al-Kuraya, Khawla
AU - Schraml, Peter
AU - Torhorst, Joachim
AU - Tapia, Coya
AU - Zaharieva, Boriana
AU - Novotny, Hedvika
AU - Spichtin, Hanspeter
AU - Maurer, Robert
AU - Mirlacher, Martina
AU - Köchli, Ossi
AU - Zuber, Markus
AU - Dieterich, Holger
AU - Mross, Friedrich
AU - Wilber, Kim
AU - Simon, Ronald
AU - Sauter, Guido
PY - 2004
Y1 - 2004
N2 - Multiple different oncogenes have been described previously to be amplified in breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability. As such, presence of one or several gene amplifications may have prognostic significance. To assess the prognostic importance of amplifications and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow-up information. Fluorescence in situ hybridizations revealed amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and EGFR in 0.8% of the tumors. All gene amplifications were significantly associated with high grade. HER2 (P <0.001) and MYC amplification (P <0.001) were also linked to shortened survival. In case of HER2, this was independent of grade, pT, and pN categories. MYC amplification was almost 3 times more frequent in medullary cancer (15.9%), than in the histologic subtype with the second highest frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated with estrogen receptor/progesterone receptor negativity (P <0.001) whereas CCND1 amplification was linked to estrogen receptor/progesterone receptor positivity (P <0.001). Coamplifications were more prevalent than expected based on the individual frequencies. Coamplifications of one or several other oncogenes occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than tumors with only one of these amplifications. Furthermore, a gradual decrease of survival was observed with increasing number of amplifications. In conclusion, these data support a major prognostic impact of genomic instability as determined by a broad gene amplification survey in breast cancer.
AB - Multiple different oncogenes have been described previously to be amplified in breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability. As such, presence of one or several gene amplifications may have prognostic significance. To assess the prognostic importance of amplifications and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow-up information. Fluorescence in situ hybridizations revealed amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and EGFR in 0.8% of the tumors. All gene amplifications were significantly associated with high grade. HER2 (P <0.001) and MYC amplification (P <0.001) were also linked to shortened survival. In case of HER2, this was independent of grade, pT, and pN categories. MYC amplification was almost 3 times more frequent in medullary cancer (15.9%), than in the histologic subtype with the second highest frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated with estrogen receptor/progesterone receptor negativity (P <0.001) whereas CCND1 amplification was linked to estrogen receptor/progesterone receptor positivity (P <0.001). Coamplifications were more prevalent than expected based on the individual frequencies. Coamplifications of one or several other oncogenes occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than tumors with only one of these amplifications. Furthermore, a gradual decrease of survival was observed with increasing number of amplifications. In conclusion, these data support a major prognostic impact of genomic instability as determined by a broad gene amplification survey in breast cancer.
M3 - SCORING: Zeitschriftenaufsatz
VL - 64
SP - 8534
EP - 8540
JO - CANCER RES
JF - CANCER RES
SN - 0008-5472
IS - 23
M1 - 23
ER -