CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

Autor: Laura M. Wastall, Christian Scerri, Godfrey Grech, Christian Saliba, Angelene Berwick, Thomas A. Hughes, Valerie Speirs, Shawn Baldacchino, Andrew M. Hanby
Rok vydání: 2017
Předmět:
0301 basic medicine
Oncology
medicine.medical_specialty
Multivariate analysis
medicine.medical_treatment
Breast Neoplasms
Autoantigens
Disease-Free Survival
Metastasis
Estrogen -- Antagonists -- Therapeutic use
03 medical and health sciences
0302 clinical medicine
Breast cancer
Internal medicine
Myc proteins
medicine
Humans
Drug resistance in cancer cells
RC254-282
Tissue microarray
Breast -- Cancer -- Treatment
business.industry
Intracellular Signaling Peptides and Proteins
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Membrane Proteins
General Medicine
Protein phosphatase 2
medicine.disease
Prognosis
Immunohistochemistry
Tamoxifen
030104 developmental biology
Receptors
Estrogen
030220 oncology & carcinogenesis
Tamoxifen -- Therapeutic use
Female
Neoplasm Recurrence
Local
business
Adjuvant
medicine.drug
Zdroj: Tumor Biology, Vol 39 (2017)
ISSN: 1423-0380
1010-4283
Popis: CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor–positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor–positive breast cancer.
peer-reviewed
Databáze: OpenAIRE
Externí odkaz: