Cyclin D1 gene amplification is highly homogeneous in breast cancer
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Cyclin D1 gene amplification is highly homogeneous in breast cancer. / Burandt, Eike; Grünert , Martin ; Lebeau, Annette; Choschzick, Matthias; Quaas, Alexander; Jänicke, Fritz; Müller, Volkmar; Scholz, Ursula; Bokemeyer, Carsten; Petersen, Cordula; Geist, Stefan; Paluchowski, Peter; Wilke, Christian; Heilenkötter, Uwe; Simon, Ronald; Sauter, Guido; Wilczak, Waldemar.
in: BREAST CANCER-TOKYO, Jahrgang 23, Nr. 1, 01.2016, S. 111-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Cyclin D1 gene amplification is highly homogeneous in breast cancer
AU - Burandt, Eike
AU - Grünert , Martin
AU - Lebeau, Annette
AU - Choschzick, Matthias
AU - Quaas, Alexander
AU - Jänicke, Fritz
AU - Müller, Volkmar
AU - Scholz, Ursula
AU - Bokemeyer, Carsten
AU - Petersen, Cordula
AU - Geist, Stefan
AU - Paluchowski, Peter
AU - Wilke, Christian
AU - Heilenkötter, Uwe
AU - Simon, Ronald
AU - Sauter, Guido
AU - Wilczak, Waldemar
PY - 2016/1
Y1 - 2016/1
N2 - BACKGROUND: Cyclin D1 (CCND1) gene amplification is a molecular key alteration in breast cancer and was suggested to predict resistance to antihormonal therapy. As tissue heterogeneity may affect diagnostic accuracy of predictive biomarkers, CCND1 genetic heterogeneity was assessed in this study. A novel tissue microarray (TMA) platform was manufactured for this purpose.METHODS: Primary breast carcinomas from 147 patients were sampled in a "heterogeneity-TMA" by taking eight different tissue cores from 4 to 8 tumor-containing blocks per case. Additional tissue samples were taken from 1 to 4 corresponding nodal metastases in 35 of these patients. CCND1 amplification was assessed by fluorescence in situ hybridization (FISH).RESULTS: CCND1 amplification was seen in 28 of 133 (21.05 %) informative patients. Amplification was significantly associated with high tumor grade (p = 0.042), but unrelated to tumor type (p = 0.307), stage (p = 0.540) and ER (p = 0.061) or PR (p = 0.871) expression. A discordant Cyclin D1 amplification status was detected in 6 out of 28 (21.43 %) amplified tumors by heterogeneity-TMA analysis. Re-testing on large sections revealed three patients with true heterogeneity of high-level CCND1 amplification and another three patients with variable interpretation of borderline FISH ratios ranging between 1.7 and 2.3. No discrepancies were detected between 22 primary tumors and their matched lymph node metastases.CONCLUSIONS: The high degree of homogeneity seen for CCND1 amplification suggests that this alteration is an early event in the development of a small subset of breast cancers.
AB - BACKGROUND: Cyclin D1 (CCND1) gene amplification is a molecular key alteration in breast cancer and was suggested to predict resistance to antihormonal therapy. As tissue heterogeneity may affect diagnostic accuracy of predictive biomarkers, CCND1 genetic heterogeneity was assessed in this study. A novel tissue microarray (TMA) platform was manufactured for this purpose.METHODS: Primary breast carcinomas from 147 patients were sampled in a "heterogeneity-TMA" by taking eight different tissue cores from 4 to 8 tumor-containing blocks per case. Additional tissue samples were taken from 1 to 4 corresponding nodal metastases in 35 of these patients. CCND1 amplification was assessed by fluorescence in situ hybridization (FISH).RESULTS: CCND1 amplification was seen in 28 of 133 (21.05 %) informative patients. Amplification was significantly associated with high tumor grade (p = 0.042), but unrelated to tumor type (p = 0.307), stage (p = 0.540) and ER (p = 0.061) or PR (p = 0.871) expression. A discordant Cyclin D1 amplification status was detected in 6 out of 28 (21.43 %) amplified tumors by heterogeneity-TMA analysis. Re-testing on large sections revealed three patients with true heterogeneity of high-level CCND1 amplification and another three patients with variable interpretation of borderline FISH ratios ranging between 1.7 and 2.3. No discrepancies were detected between 22 primary tumors and their matched lymph node metastases.CONCLUSIONS: The high degree of homogeneity seen for CCND1 amplification suggests that this alteration is an early event in the development of a small subset of breast cancers.
U2 - 10.1007/s12282-014-0538-y
DO - 10.1007/s12282-014-0538-y
M3 - SCORING: Journal article
C2 - 24862872
VL - 23
SP - 111
EP - 119
JO - BREAST CANCER-TOKYO
JF - BREAST CANCER-TOKYO
SN - 1340-6868
IS - 1
ER -