Investigation of molecular alterations ofAKT-3in triple-negative breast cancer
| Autor: | Robert Cummins, Cecily Quinn, Etáin Daly, Aisling Pierce, Michael J. Duffy, Elaine W. Kay, Yue Fan, Mairin Rafferty, Dara M. FitzGerald, Miriam A Lynn, Fredrik Pontén, Louise Flanagan, Anthony O'Grady, Gillian O'Hurley, Karin Jirström, William M. Gallagher |
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| Rok vydání: | 2013 |
| Předmět: |
Histology
Gene Dosage Estrogen receptor Breast Neoplasms Triple Negative Breast Neoplasms Kaplan-Meier Estimate Negative association Bioinformatics Disease-Free Survival Pathology and Forensic Medicine Cohort Studies Breast cancer Biomarkers Tumor Humans Medicine Protein kinase B In Situ Hybridization Fluorescence Survival analysis Triple-negative breast cancer medicine.diagnostic_test business.industry Incidence (epidemiology) Gene Amplification General Medicine medicine.disease Immunohistochemistry Receptors Estrogen Cancer research Female business Proto-Oncogene Proteins c-akt Fluorescence in situ hybridization |
| Zdroj: | Histopathology. 64:660-670 |
| ISSN: | 0309-0167 |
| DOI: | 10.1111/his.12313 |
| Popis: | Aims Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer (BC) deaths, owing to its intrinsic aggressiveness and a lack of treatment options, especially targeted therapies. Thus, there is an urgent need for the development of better targeted treatments for TNBC. Molecular alteration of AKT-3 was previously reported in oestrogen receptor (ER)-positive BC. AKT-3 has also been suggested to play a role in hormone-unresponsive BC. The aim of this study was to investigate molecular alterations of AKT-3 in TNBC, to perform associated survival analysis, and to compare these findings with the incidence of AKT-3 molecular alterations in ER-positive BC. Results Our study revealed AKT-3 amplification and deletions in 11% (9/82) and 13% (11/82) of TNBCs, respectively. In contrast, 1% (2/209) of ER-positive BCs were found to have AKT-3 amplifications and deletions. A higher prevalence of AKT-3 copy number gains was observed in TNBC [26% (21/82)] than in ER-positive BC [9% (19/209)]. AKT-3 amplification together with Akt-3 protein expression was negatively associated with recurrence-free survival in TNBC. Furthermore, a negative association between high AKT-3 copy number and recurrence-free survival was observed. Conclusion AKT-3 amplification could represent a potentially relevant oncogenic event in a subset of TNBCs that may, in turn, select cells sensitive to Akt-3 inhibitors. |
| Databáze: | OpenAIRE |
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