CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

Shawn Baldacchino, Laura M Wastall, Christian Saliba, Thomas A Hughes, Christian Scerri, Angelene Berwick, Valerie Speirs, Andrew M Hanby, Godfrey Grech

Research output: Contribution to journalArticle

3 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)1010428317722064
JournalTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
Volume39
Issue number10
DOIs
Publication statusPublished - Oct 2017

Fingerprint

Tamoxifen
Breast Neoplasms
Recurrence
Estrogen Receptors
Disease-Free Survival
Tissue Banks
Protein Phosphatase 2
Epithelial-Mesenchymal Transition
Oncogene Proteins
Neoplasms
Therapeutics
Multivariate Analysis
Immunohistochemistry
Staining and Labeling
Neoplasm Metastasis
Proteins

Keywords

  • Autoantigens
  • Breast Neoplasms
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Membrane Proteins
  • Neoplasm Recurrence, Local
  • Prognosis
  • Receptors, Estrogen
  • Tamoxifen
  • Journal Article

Cite this

CIP2A expression predicts recurrences of tamoxifen-treated breast cancer. / Baldacchino, Shawn; Wastall, Laura M; Saliba, Christian; Hughes, Thomas A; Scerri, Christian; Berwick, Angelene; Speirs, Valerie; Hanby, Andrew M; Grech, Godfrey.

In: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, Vol. 39, No. 10, 10.2017, p. 1010428317722064.

Research output: Contribution to journalArticle

Baldacchino, Shawn ; Wastall, Laura M ; Saliba, Christian ; Hughes, Thomas A ; Scerri, Christian ; Berwick, Angelene ; Speirs, Valerie ; Hanby, Andrew M ; Grech, Godfrey. / CIP2A expression predicts recurrences of tamoxifen-treated breast cancer. In: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2017 ; Vol. 39, No. 10. pp. 1010428317722064.
@article{3b8346990c8d4d129fc49c5ccd66b242,
title = "CIP2A expression predicts recurrences of tamoxifen-treated breast cancer",
abstract = "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.",
keywords = "Autoantigens, Breast Neoplasms, Disease-Free Survival, Female, Humans, Immunohistochemistry, Membrane Proteins, Neoplasm Recurrence, Local, Prognosis, Receptors, Estrogen, Tamoxifen, Journal Article",
author = "Shawn Baldacchino and Wastall, {Laura M} and Christian Saliba and Hughes, {Thomas A} and Christian Scerri and Angelene Berwick and Valerie Speirs and Hanby, {Andrew M} and Godfrey Grech",
year = "2017",
month = "10",
doi = "10.1177/1010428317722064",
language = "English",
volume = "39",
pages = "1010428317722064",
journal = "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine",
issn = "1010-4283",
publisher = "SAGE Publications Inc.",
number = "10",

}

TY - JOUR

T1 - CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

AU - Baldacchino, Shawn

AU - Wastall, Laura M

AU - Saliba, Christian

AU - Hughes, Thomas A

AU - Scerri, Christian

AU - Berwick, Angelene

AU - Speirs, Valerie

AU - Hanby, Andrew M

AU - Grech, Godfrey

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Autoantigens

KW - Breast Neoplasms

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Membrane Proteins

KW - Neoplasm Recurrence, Local

KW - Prognosis

KW - Receptors, Estrogen

KW - Tamoxifen

KW - Journal Article

U2 - 10.1177/1010428317722064

DO - 10.1177/1010428317722064

M3 - Article

C2 - 29034804

VL - 39

SP - 1010428317722064

JO - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

JF - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

SN - 1010-4283

IS - 10

ER -