Cytoplasmic Cyclin E Predicts Recurrence in Patients with Breast Cancer
| Autor: | Anna Biernacka, Min Yi, W. Fraser Symmans, Kwok-Leung Cheung, Cansu Karakas, Opoku Adjapong, Kim Anh Do, Gabriel N. Hortobagyi, Sarah S. Bacus, Khandan Keyomarsi, Kelly K. Hunt, Melissa L. Bondy, Ian O. Ellis, Min Jin Ha, Patricia A. Thompson, Aysegul A. Sahin |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
0301 basic medicine Cytoplasm Cancer Research Pathology medicine.medical_specialty Cyclin E Breast Neoplasms Biology Disease-Free Survival Article 03 medical and health sciences 0302 clinical medicine Breast cancer Western blot Cell Line Tumor Biomarkers Tumor medicine Humans Protein Isoforms Prospective cohort study Aged Cyclin Aged 80 and over Cell Nucleus medicine.diagnostic_test Cancer Middle Aged Prognosis medicine.disease Subcellular localization 3. Good health Molecular Weight 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Female Neoplasm Recurrence Local Cytoplasmic cyclin E breast cancer biomarker cell cycle |
| Zdroj: | Clinical Cancer Research. 23:2991-3002 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Low molecular weight cyclin E (LMW-E) detected by Western blot analysis predicts for reduced breast cancer survival; however, it is impractical for clinical use. LMW-E lacks a nuclear localization signal that leads to accumulation in the cytoplasm that can be detected by IHC. We tested the hypothesis that cytoplasmic staining of cyclin E can be used as a predictor of poor outcome in different subtypes of breast cancer using patient cohorts with distinct clinical and pathologic features.Experimental Design: We evaluated the subcellular localization of cyclin E in breast cancer specimens from 2,494 patients from 4 different cohorts: 303 from a prospective study and 2,191 from retrospective cohorts [NCI, MD Anderson Cancer Center (MDA), and the United Kingdom (UK)]. Median follow-up times were 8.0, 10.1, 13.5, and 5.7 years, respectively.Results: Subcellular localization of cyclin E on IHC was associated with full-length (nuclear) and low molecular weight isoforms (cytoplasmic) of cyclin E on Western blot analysis. In multivariable analysis, cytoplasmic cyclin E staining was associated with the greatest risk of recurrence compared with other prognostic factors across all subtypes in three (NCI, MDA, and UK) of the cohorts. In the MDA cohort, cytoplasmic cyclin E staining outperformed Ki67 and all other variables as prognostic factors.Conclusions: Cytoplasmic cyclin E identifies patients with the highest likelihood of recurrence consistently across different patient cohorts and subtypes. These patients may benefit from alternative therapies targeting the oncogenic isoforms of cyclin E. Clin Cancer Res; 23(12); 2991–3002. ©2016 AACR. |
| Databáze: | OpenAIRE |
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