The prognostic significance of wild type isocitrate dehydrogenase 2 (IDH2) in breast cancer

Aljohani, Abrar I; Toss, Michael S; Kurozumi, Sasagu; Joseph, Chitra; Aleskandarany, Mohammed A; Miligy, Islam M; Ansari, Rokaya El; Mongan, Nigel P; Ellis, Ian O; Green, Andrew R; Rakha, Emad

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 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.

Citation

Aljohani, A. I., Toss, M. S., Kurozumi, S., Joseph, C., Aleskandarany, M. A., Miligy, I. M., Ansari, R. E., Mongan, N. P., Ellis, I. O., Green, A. R., & Rakha, E. (2020). The prognostic significance of wild type isocitrate dehydrogenase 2 (IDH2) in breast cancer. Breast Cancer Research and Treatment, 179(1), 79–90. https://doi.org/10.1007/s10549-019-05459-7

• Journal Article Type: Article
• Acceptance Date: Sep 25, 2019
• Online Publication Date: Oct 10, 2019
• Publication Date: 2020-01
• Deposit Date: Sep 30, 2019
• Publicly Available Date: Oct 11, 2020
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 179
• Issue: 1
• Pages: 79–90
• DOI: https://doi.org/10.1007/s10549-019-05459-7
• Keywords: IDH2; breast cancer; progression; LVI; prognosis
• Public URL: https://nottingham-repository.worktribe.com/output/2721139
• Publisher URL: https://link.springer.com/article/10.1007/s10549-019-05459-7
• Additional Information: Received: 18 September 2019; Accepted: 25 September 2019; First Online: 10 October 2019; : ; : All authors declare that they have no conflict of interest.; : This article does not contain any studies with human participants or animals performed by any of the authors.; : This work obtained ethics approval to use the human tissue samples by the North West – Greater Manchester Central Research Ethics Committee under the title Nottingham Health Science Biobank (NHSB), reference number 15/NW/0685. Informed consent was obtained from all individuals prior to surgery to use their tissue materials in research. This study was performed according to the REMARK guidelines for tumour prognostic studies.
• Contract Date: Sep 30, 2019