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01-01-2016 | Original Article

Cyclin D1 gene amplification is highly homogeneous in breast cancer

Authors: Eike Burandt, Martin Grünert, Annette Lebeau, Matthias Choschzick, Alexander Quaas, Fritz Jänicke, Volkmar Müller, Ursula Scholz, Carsten Bokemeyer, Cordula Petersen, Stefan Geist, Peter Paluchowski, Christian Wilke, Uwe Heilenkötter, Ronald Simon, Guido Sauter, Waldemar Wilczak

Published in: Breast Cancer | Issue 1/2016

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.

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Title: Cyclin D1 gene amplification is highly homogeneous in breast cancer
Authors: Eike Burandt
Martin Grünert
Annette Lebeau
Matthias Choschzick
Alexander Quaas
Fritz Jänicke
Volkmar Müller
Ursula Scholz
Carsten Bokemeyer
Cordula Petersen
Stefan Geist
Peter Paluchowski
Christian Wilke
Uwe Heilenkötter
Ronald Simon
Guido Sauter
Waldemar Wilczak
Publication date: 01-01-2016
Publisher: Springer Japan
Published in: Breast Cancer / Issue 1/2016
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI: https://doi.org/10.1007/s12282-014-0538-y

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