2021年7月
Isoforms of IDH in breast carcinoma: IDH2 as a potent prognostic factor associated with proliferation in estrogen-receptor positive cases.
Breast cancer (Tokyo, Japan)
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- 巻
- 28
- 号
- 4
- 開始ページ
- 915
- 終了ページ
- 926
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1007/s12282-021-01228-x
BACKGROUND: Isocitrate dehydrogenase (IDH) is an important enzyme that oxidatively decarboxylates isocitrate to α-ketoglutarate, and three isoforms (IDH1-3) have been identified. Overexpression and/or downregulation of IDH isoforms was reported in several human malignancies, suggesting importance of IDH in oncogenesis. However, significance of IDH isoforms remains largely unclear in the breast carcinoma. METHODS: We immunolocalized IDH1, IDH2 and IDH3α in 226 breast carcinomas and evaluated their clinical significance. Subsequently, we examined effects of IDH2 on proliferation in breast carcinoma cells. RESULTS: Immunoreactivity of IDH1-3α was detected in 53%, 38% and 41% of breast carcinomas, and the non-neoplastic epithelium was IDH1-positive, IDH2-negative and IDH3α-positive. IDH1 immunoreactivity was inversely associated with pathological T factor (pT) and Ki-67 in the breast carcinoma, while IDH3α immunoreactivity was not significantly associated with clinicopathological factors. IDH2 status was positively correlated with stage, pT, histological grade, HER2, Ki-67 and microvessel density. Moreover, IDH2 status was significantly associated with worse prognosis of the patients, and it turned out an independent prognostic factor for estrogen-receptor (ER) positive patients. These findings were more evident in the IDH1-negative / IDH2-positive/IDH3α-negative subgroup which is the opposite immunohistochemical IDH phenotype of normal mammary epithelium. In vitro studies demonstrated that RNA interference of IDH2 significantly decreased proliferation activity of T47D and SKBR-3 cells. CONCLUSION: These results suggest that IDH2 is associated with an aggressive phenotype of breast carcinoma through increasing cell proliferation, different from IDH1 and IDH3α, and immunohistochemical IDH2 status is a potent prognostic factor especially in ER-positive breast cancer patients.
- リンク情報
- ID情報
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- DOI : 10.1007/s12282-021-01228-x
- PubMed ID : 33713004