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

被引：20

作者：

Aljohani, Abrar I. ^{[1
]}

Toss, Michael S. ^{[1
]}

Kurozumi, Sasagu ^{[1
]}

Joseph, Chitra ^{[1
]}

Aleskandarany, Mohammed A. ^{[1
]}

Miligy, Islam M. ^{[1
,2
]}

Ansari, Rokaya El ^{[1
]}

Mongan, Nigel P. ^{[3
,4
]}

Ellis, Ian O. ^{[1
]}

Green, Andrew R. ^{[1
]}

Rakha, Emad A. ^{[1
,2
,5
]}

机构：

[1] Univ Nottingham, Sch Med, Nottingham Breast Canc Res Ctr, Div Canc & Stem Cells, Nottingham, England

[2] Menoufia Univ, Fac Med, Histopathol Dept, Shibin Al Kawm, Egypt

[3] Weill Cornell Med, Dept Pharmacol, New York, NY 10065 USA

[4] Univ Nottingham, Fac Med & Hlth Sci, Nottingham LE12 5RD, England

[5] Nottingham Univ Hosp NHS Trust, Dept Histopathol, City Hosp Campus,Hucknall Rd, Nottingham NG5 1PB, England

来源：

BREAST CANCER RESEARCH AND TREATMENT | 2020年 / 179卷 / 01期

关键词：

IDH2; Breast cancer; Progression; LVI; Prognosis; EPITHELIAL-MESENCHYMAL TRANSITION; LYMPHOVASCULAR INVASION; N-CADHERIN; EXPRESSION; METABOLISM; HALLMARK; SUBTYPE; SERIES; KEY;

D O I：

10.1007/s10549-019-05459-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：79 / 90

页数：12

共 48 条

[1] 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 analyses [J].

Abd El-Rehim, DM ;

Ball, G ;

Pinder, SE ;

Rakha, E ;

Paish, C ;

Robertson, JFR ;

Macmillan, D ;

Blamey, RW ;

Ellis, IO .

INTERNATIONAL JOURNAL OF CANCER, 2005, 116 (03) :340-350

[2] Molecular Mechanisms Underlying Lymphovascular Invasion in Invasive Breast Cancer [J].

Aleskandarany, Mohammed A. ;

Sonbul, Sultan N. ;

Mukherjee, Abhik ;

Rakha, Emad A. .

PATHOBIOLOGY, 2015, 82 (3-4) :113-123

[3] Clinicopathologic and molecular significance of phospho-Akt expression in early invasive breast cancer [J].

Aleskandarany, Mohammed A. ;

Rakha, Emad A. ;

Ahmed, Mohamed A. ;

Powe, Desmond G. ;

Ellis, Ian O. ;

Green, Andrew R. .

BREAST CANCER RESEARCH AND TREATMENT, 2011, 127 (02) :407-416

[4] Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists [J].

Badve, Sunil ;

Dabbs, David J. ;

Schnitt, Stuart J. ;

Baehner, Frederick L. ;

Decker, Thomas ;

Eusebi, Vincenzo ;

Fox, Stephen B. ;

Ichihara, Shu ;

Jacquemier, Jocelyne ;

Lakhani, Sunil R. ;

Palacios, Jose ;

Rakha, Emad A. ;

Richardson, Andrea L. ;

Schmitt, Fernando C. ;

Tan, Puay-Hoon ;

Tse, Gary M. ;

Weigelt, Britta ;

Ellis, Ian O. ;

Reis-Filho, Jorge S. .

MODERN PATHOLOGY, 2011, 24 (02) :157-167

[5] The prognostic value of regulatory T cells infiltration in HER2-enriched breast cancer microenvironment [J].

Banin-Hirata, Bruna K. ;

de Oliveira, Carlos E. C. ;

Losi-Guembarovski, Roberta ;

Ozawa, Patricia M. M. ;

Vitiello, Glauco A. F. ;

de Almeida, Felipe C. ;

Derossi, Daniela R. ;

Andre, Nayara D. ;

Watanabe, Maria A. E. .

INTERNATIONAL REVIEWS OF IMMUNOLOGY, 2018, 37 (03) :144-150

[6] Wild-Type IDH Enzymes as Actionable Targets for Cancer Therapy [J].

Bergaggio, Elisa ;

Piva, Roberto .

CANCERS, 2019, 11 (04)

[7] Cancer Cell Metabolism: One Hallmark, Many Faces [J].

Cantor, Jason R. ;

Sabatini, David M. .

CANCER DISCOVERY, 2012, 2 (10) :881-898

[8] IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity [J].

Chiang, Sarah ;

Weigelt, Britta ;

Wen, Huei-Chi ;

Pareja, Fresia ;

Raghavendra, Ashwini ;

Martelotto, Luciano G. ;

Burke, Kathleen A. ;

Basili, Thais ;

Li, Anqi ;

Geyer, Felipe C. ;

Piscuoglio, Salvatore ;

Ng, Charlotte K. Y. ;

Jungbluth, Achim A. ;

Balss, Joerg ;

Pusch, Stefan ;

Baker, Gabrielle M. ;

Cole, Kimberly S. ;

von Deimling, Andreas ;

Batten, Julie M. ;

Marotti, Jonathan D. ;

Soh, Hwei-Choo ;

McCalip, Benjamin L. ;

Serrano, Jonathan ;

Lim, Raymond S. ;

Siziopikou, Kalliopi P. ;

Lu, Song ;

Liu, Xiaolong ;

Hammour, Tarek ;

Brogi, Edi ;

Snuderl, Matija ;

Iafrate, A. John ;

Reis-Filho, Jorge S. ;

Schnitt, Stuart J. .

CANCER RESEARCH, 2016, 76 (24) :7118-7129

[9] Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer [J].

Ciriello, Giovanni ;

Gatza, Michael L. ;

Beck, Andrew H. ;

Wilkerson, Matthew D. ;

Rhie, Suhn K. ;

Pastore, Alessandro ;

Zhang, Hailei ;

McLellan, Michael ;

Yau, Christina ;

Kandoth, Cyriac ;

Bowlby, Reanne ;

Shen, Hui ;

Hayat, Sikander ;

Fieldhouse, Robert ;

Lester, Susan C. ;

Tse, Gary M. K. ;

Factor, Rachel E. ;

Collins, Laura C. ;

Allison, Kimberly H. ;

Chen, Yunn-Yi ;

Jensen, Kristin ;

Johnson, Nicole B. ;

Oesterreich, Steffi ;

Mills, Gordon B. ;

Cherniack, Andrew D. ;

Robertson, Gordon ;

Benz, Christopher ;

Sander, Chris ;

Laird, Peter W. ;

Hoadley, Katherine A. ;

King, Tari A. ;

Perou, Charles M. .

CELL, 2015, 163 (02) :506-519

[10] MYC regulation of glutamine-proline regulatory axis is key in luminal B breast cancer [J].

Craze, Madeleine L. ;

Cheung, Hayley ;

Jewa, Natasha ;

Coimbra, Nuno D. M. ;

Soria, Daniele ;

El-Ansari, Rokaya ;

Aleskandarany, Mohammed A. ;

Cheng, Kiu Wai ;

Diez-Rodriguez, Maria ;

Nolan, Christopher C. ;

Ellis, Ian O. ;

Rakha, Emad A. ;

Green, Andrew R. .

BRITISH JOURNAL OF CANCER, 2018, 118 (02) :258-265

← 1 2 3 4 5 →