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, Vol. 23, No. 1, 01.2016, p. 111-9.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

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Burandt, E, Grünert , M, Lebeau, A, Choschzick, M, Quaas, A, Jänicke, F, Müller, V, Scholz, U, Bokemeyer, C, Petersen, C, Geist, S, Paluchowski, P, Wilke, C, Heilenkötter, U, Simon, R, Sauter, G & Wilczak, W 2016, 'Cyclin D1 gene amplification is highly homogeneous in breast cancer', BREAST CANCER-TOKYO, vol. 23, no. 1, pp. 111-9. https://doi.org/10.1007/s12282-014-0538-y

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@article{7db8ff12c5cd4ce181f8694368432a14,
title = "Cyclin D1 gene amplification is highly homogeneous in breast cancer",
abstract = "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.",
author = "Eike Burandt and Martin Gr{\"u}nert and Annette Lebeau and Matthias Choschzick and Alexander Quaas and Fritz J{\"a}nicke and Volkmar M{\"u}ller and Ursula Scholz and Carsten Bokemeyer and Cordula Petersen and Stefan Geist and Peter Paluchowski and Christian Wilke and Uwe Heilenk{\"o}tter and Ronald Simon and Guido Sauter and Waldemar Wilczak",
year = "2016",
month = jan,
doi = "10.1007/s12282-014-0538-y",
language = "English",
volume = "23",
pages = "111--9",
journal = "BREAST CANCER-TOKYO",
issn = "1340-6868",
publisher = "Springer Japan",
number = "1",

}

RIS

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 -