Cyclin D1 gene amplification is highly homogeneous in breast cancer. 2016

Eike Burandt, and Martin Grünert, and Annette Lebeau, and Matthias Choschzick, and Alexander Quaas, and Fritz Jänicke, and Volkmar Müller, and Ursula Scholz, and Carsten Bokemeyer, and Cordula Petersen, and Stefan Geist, and Peter Paluchowski, and Christian Wilke, and Uwe Heilenkötter, and Ronald Simon, and Guido Sauter, and Waldemar Wilczak
Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. e.burandt@uke.de.

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.

UI MeSH Term Description Entries
D009367 Neoplasm Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260 Female Females
D005784 Gene Amplification A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. Amplification, Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017404 In Situ Hybridization, Fluorescence A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. FISH Technique,Fluorescent in Situ Hybridization,Hybridization in Situ, Fluorescence,FISH Technic,Hybridization in Situ, Fluorescent,In Situ Hybridization, Fluorescent,FISH Technics,FISH Techniques,Technic, FISH,Technics, FISH,Technique, FISH,Techniques, FISH
D046888 Tissue Array Analysis The simultaneous analysis of multiple samples of TISSUES or CELLS from BIOPSY or in vitro culture that have been arranged in an array format on slides or microchips. Cell Array Analysis,Cell Microarray Analysis,Tissue Microarray Analysis,Analyses, Cell Array,Analyses, Cell Microarray,Analyses, Tissue Array,Analyses, Tissue Microarray,Analysis, Cell Array,Analysis, Cell Microarray,Analysis, Tissue Array,Analysis, Tissue Microarray,Array Analyses, Cell,Array Analyses, Tissue,Array Analysis, Cell,Array Analysis, Tissue,Cell Array Analyses,Cell Microarray Analyses,Microarray Analyses, Cell,Microarray Analyses, Tissue,Microarray Analysis, Cell,Microarray Analysis, Tissue,Tissue Array Analyses,Tissue Microarray Analyses
D060787 Neoplasm Grading Methods which attempt to express in replicable terms the level of CELL DIFFERENTIATION in neoplasms as increasing ANAPLASIA correlates with the aggressiveness of the neoplasm. Gleason Grading,Gleason Score,Tumor Grading,Grading, Gleason,Grading, Neoplasm,Grading, Tumor,Score, Gleason
D018275 Carcinoma, Lobular A type of BREAST CANCER where the abnormal malignant cells form in the lobules, or milk-producing glands, of the breast. Carcinomas, Lobular,Lobular Carcinoma,Lobular Carcinomas
D019938 Cyclin D1 Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms. CCND1 Protein,PRAD1 Protein,Proto-Oncogene Proteins c-bcl-1,bcl-1 Proto-Oncogene Proteins,c-bcl-1 Proteins,Proto-Oncogene Products bcl-1,Proto-Oncogene Protein bcl-1,bcl-1 Proto-Oncogene Products,bcl1 Proto-Oncogene Proteins,Proto Oncogene Products bcl 1,Proto Oncogene Protein bcl 1,Proto Oncogene Proteins c bcl 1,Proto-Oncogene Products, bcl-1,Proto-Oncogene Proteins, bcl-1,Proto-Oncogene Proteins, bcl1,bcl 1 Proto Oncogene Products,bcl 1 Proto Oncogene Proteins,bcl-1, Proto-Oncogene Protein,bcl1 Proto Oncogene Proteins,c bcl 1 Proteins,c-bcl-1, Proto-Oncogene Proteins

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