The prognostic significance of wild-type isocitrate dehydrogenase 2 (IDH2) in breast cancer
Open Access
- 10 October 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Breast Cancer Research and Treatment
- Vol. 179 (1), 79-90
- https://doi.org/10.1007/s10549-019-05459-7
Abstract
Background Lymphovascular invasion (LVI) is a prerequisite step in breast cancer (BC) metastasis. We have previously identified wild-type isocitrate dehydrogenase 2 (IDH2) as a key putative driver of LVI. Thus, we explored the prognostic significance of IDH2 at transcriptome and protein expression levels in pre-invasive and invasive disease. Methods Utlising tissue microarrays from a large well annotated BC cohort including ductal carcinoma in situ and invasive breast cancer (IBC), IDH2 was assessed at the transcriptomic and proteomic level. The associations between clinicopathological factors including LVI status, prognosis and the expression of IDH2 were evaluated. Results In pure DCIS and IBC, high IDH2 protein expression was associated with features of aggressiveness including high nuclear grade, larger size, comedo necrosis and hormonal receptor negativity and LVI, higher grade, larger tumour size, high NPI, HER2 positivity, and hormonal receptor negativity, respectively. High expression of IDH2 either in mRNA or in protein levels was associated with poor patient’s outcome in both DCIS and IBC. Multivariate analysis revealed that IDH2 protein expression was an independent risk factor for shorter BC specific-survival. Conclusion Further functional studies to decipher the role of IDH2 and its mechanism of action as a driver of BC progression and LVI are warranted.Keywords
This publication has 50 references indexed in Scilit:
- Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registryBreast Cancer Research and Treatment, 2013
- Cancer Cell Metabolism: One Hallmark, Many FacesCancer Discovery, 2012
- Altered expression levels of IDH2 are involved in the development of colon cancerExperimental and Therapeutic Medicine, 2012
- The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroupsNature, 2012
- Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not AnticipateCancer Cell, 2012
- Basal keratin expression in breast cancer by quantification of mRNA and by immunohistochemistryJournal of Experimental & Clinical Cancer Research, 2010
- Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicityProceedings of the National Academy of Sciences of the United States of America, 2010
- A weighted average difference method for detecting differentially expressed genes from microarray dataAlgorithms for Molecular Biology, 2008
- Mechanisms of metastasisBreast Cancer Research, 2008
- High‐throughput protein expression analysis using tissue microarray technology of a large well‐characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analysesInternational Journal of Cancer, 2005