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

• Published in: Breast cancer research and treatment 2020-01, Vol.179 (1), p.79-90
• Main Authors: 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 A.
• Format: Article
• Language: English
• Subjects: Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer research; Carcinoma, Intraductal, Noninfiltrating - genetics; Carcinoma, Intraductal, Noninfiltrating - metabolism; Carcinoma, Intraductal, Noninfiltrating - pathology; Comedones; Dehydrogenases; ErbB-2 protein; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; IDH2 protein; Invasiveness; Isocitrate dehydrogenase; Isocitrate Dehydrogenase - genetics; Isocitrate Dehydrogenase - metabolism; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Multivariate Analysis; Neoplasm Grading; Neoplasm Invasiveness; Oncology; Preclinical Study; Prognosis; Protein expression; Proteins; Proteomics; Risk factors; Survival Analysis; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-019-05459-7

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.