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Cyclin D1 gene amplification is highly homogeneous in breast cancer

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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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Acknowledgments

The authors appreciate the excellent technical support of Christina Koop, Sylvia Schnöger and Sasha Eghtessadi.

Conflict of interest

The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining this article.

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Authors and Affiliations

  1. Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Eike Burandt, Martin Grünert, Annette Lebeau, Matthias Choschzick, Alexander Quaas, Ronald Simon, Guido Sauter & Waldemar Wilczak

  2. Department of Gynecology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    Fritz Jänicke, Volkmar Müller & Ursula Scholz

  3. Department of Internal Medicine II, Oncology Center, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    Carsten Bokemeyer

  4. Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    Cordula Petersen

  5. Department of Gynecology, Regio Clinic Pinneberg, 25421, Pinneberg, Germany

    Stefan Geist & Peter Paluchowski

  6. Department of Gynecology, Regio Clinic Elmshorn, 25337, Elmshorn, Germany

    Christian Wilke

  7. Department of Gynecology, Clinical Centre Itzehoe, 25524, Itzehoe, Germany

    Uwe Heilenkötter

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  1. Eike Burandt
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Corresponding author

Correspondence to Eike Burandt.

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E. Burandt and M. Grünert have contributed equally to this work.

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Burandt, E., Grünert, M., Lebeau, A. et al. Cyclin D1 gene amplification is highly homogeneous in breast cancer. Breast Cancer 23, 111–119 (2016). https://doi.org/10.1007/s12282-014-0538-y

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