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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


Abrar I Aljohani

Sasagu Kurozumi

Chitra Joseph

Rokaya El Ansari

Nigel P Mongan

Andrew R Green

Emad Rakha


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.

Journal Article Type Article
Publication Date Oct 10, 2019
Journal Breast Cancer Research and Treatment
Print ISSN 0167-6806
Electronic ISSN 1573-7217
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Institution Citation Aljohani, A. I., Toss, M. S., Kurozumi, S., Joseph, C., Aleskandarany, M. A., Miligy, I. M., …Rakha, E. (2019). The prognostic significance of wild type isocitrate dehydrogenase 2 (IDH2) in breast cancer. Breast Cancer Research and Treatment,
Keywords IDH2; breast cancer; progression; LVI; prognosis
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The Prognostic Significance Of Isocitrate Dehydrogenase Final Version To BCRT 14-09-2019 (1.6 Mb)

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