8p deletion is strongly linked to poor prognosis in breast cancer
| Autor: | Sven Mahner, Katharina Möller, Stefan Geist, Cansu Özden, Patrick Lebok, Guido Sauter, Uwe Heilenkötter, A von der Assen, Rainer Krech, M. Kluth, Volkmar Müller, Annette Lebeau, Khakan Hussein, Christian Wilke, Fritz Jänicke, A Hartmann, Ronald Simon, A. Mittenzwei, Linn Wölber, Peter Paluchowski, Luigi Terracciano, E Burandt, Billurvan Taskin, Isabell Witzel |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Cancer Research Poor prognosis Pathology medicine.medical_specialty Medullary cavity Receptor ErbB-2 Genes myc Labeling index Breast Neoplasms Biology Breast cancer Cyclin D1 Tumor stage medicine Humans Clinical significance In Situ Hybridization Fluorescence Aged Aged 80 and over Pharmacology Tissue microarray Gene Amplification Middle Aged Prognosis medicine.disease Immunohistochemistry Ki-67 Antigen Oncology Tissue Array Analysis Cancer research Molecular Medicine Female Chromosome Deletion Chromosomes Human Pair 8 Research Paper |
| Zdroj: | Cancer Biology & Therapy. 16:1080-1087 |
| ISSN: | 1555-8576 1538-4047 |
| DOI: | 10.1080/15384047.2015.1046025 |
| Popis: | Deletions of chromosome 8p occur frequently in breast cancers, but analyses of its clinical relevance have been limited to small patient cohorts and provided controversial results. A tissue microarray with 2,197 breast cancers was thus analyzed by fluorescence in-situ hybridization using an 8p21 probe in combination with a centromere 8 reference probe. 8p deletions were found in 50% of carcinomas with no special type, 67% of papillary, 28% of tubular, 37% of lobular cancers and 56% of cancers with medullary features. Deletions were always heterozygous. 8p deletion was significantly linked to advanced tumor stage (P < 0.0001), high-grade (P < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; P < 0.0001), and shortened overall survival (P < 0.0001). For example, 8p deletion was seen in 32% of 290 grade 1, 43% of 438 grade 2, and 65% of 427 grade 3 cancers. In addition, 8p deletions were strongly linked to amplification of MYC (P < 0.0001), HER2 (P < 0.0001), and CCND1 (p = 0.001), but inversely associated with ER receptor expression (p = 0.0001). Remarkably, 46.5% of 8p-deleted cancers harbored amplification of at least one of the analyzed genes as compared to 27.5% amplifications in 8p-non-deleted cancers (P < 0.0001). In conclusion, 8p deletion characterizes a subset of particularly aggressive breast cancers. As 8p deletions are easy to analyze, this feature appears to be highly suited for future DNA based prognostic breast cancer panels. The strong link of 8p deletion with various gene amplifications raises the possibility of a role for regulating genomic stability. |
| Databáze: | OpenAIRE |
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