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ESPL1 is a candidate oncogene of luminal B breast cancers.
Breast Cancer Res Treat. 2014 Aug; 147(1):51-9.BC

Abstract

ESPL1/separase is a putative oncogene of luminal B breast cancers. Histoclinical correlations of its expression have never been explored in large series of breast tumors, and specifically in the luminal subtype. In a pooled series of invasive breast carcinomas profiled using DNA microarrays, we identified 3,074 luminal cases, including 1,307 luminal B tumors, in which we searched for correlations between ESPL1 mRNA expression and molecular and histoclinical features. Compared to normal breast samples, ESPL1 was overexpressed in 52 % of luminal tumors, and much more frequently in luminal B (83 %) than luminal A tumors (29 %). In luminal breast cancers, higher ESPL1 expression was associated with poor-prognosis criteria (age ≤ 50 years, ductal type, advanced stage, large tumor size, lymph node-positive status, high grade, PR-negative status, luminal B subtype) and with poor metastasis-free survival in both uni- and multivariate analyses. This independent prognostic value was also observed in luminal B tumors only, and persisted when compared with gene expression signatures (PAM50, Recurrence Score, Mammaprint, EndoPredict) currently proposed to refine the indications of adjuvant chemotherapy in hormone receptor-positive/HER2-negative breast cancer. We also confirmed the observations made with experimental mouse models: ESPL1-overexpressing luminal tumors showed complex genomic profiles and molecular features of chromosomal instability and loss of tumor suppressor genes (P53 and Rb). Our results reinforce the idea that ESPL1 is a candidate oncogene in luminal B cancers. Its expression may help improve the prognostication. Inhibiting ESPL1 may represent a promising therapeutic approach for these poor-prognosis tumors.

Authors+Show Affiliations

Department of Molecular Oncology, U1068 Inserm, Institut Paoli-Calmettes (IPC), Marseille, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25086634

Citation

Finetti, Pascal, et al. "ESPL1 Is a Candidate Oncogene of Luminal B Breast Cancers." Breast Cancer Research and Treatment, vol. 147, no. 1, 2014, pp. 51-9.
Finetti P, Guille A, Adelaide J, et al. ESPL1 is a candidate oncogene of luminal B breast cancers. Breast Cancer Res Treat. 2014;147(1):51-9.
Finetti, P., Guille, A., Adelaide, J., Birnbaum, D., Chaffanet, M., & Bertucci, F. (2014). ESPL1 is a candidate oncogene of luminal B breast cancers. Breast Cancer Research and Treatment, 147(1), 51-9. https://doi.org/10.1007/s10549-014-3070-z
Finetti P, et al. ESPL1 Is a Candidate Oncogene of Luminal B Breast Cancers. Breast Cancer Res Treat. 2014;147(1):51-9. PubMed PMID: 25086634.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ESPL1 is a candidate oncogene of luminal B breast cancers. AU - Finetti,Pascal, AU - Guille,Arnaud, AU - Adelaide,José, AU - Birnbaum,Daniel, AU - Chaffanet,Max, AU - Bertucci,François, Y1 - 2014/08/03/ PY - 2014/06/10/received PY - 2014/07/19/accepted PY - 2014/8/4/entrez PY - 2014/8/5/pubmed PY - 2015/9/22/medline SP - 51 EP - 9 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 147 IS - 1 N2 - ESPL1/separase is a putative oncogene of luminal B breast cancers. Histoclinical correlations of its expression have never been explored in large series of breast tumors, and specifically in the luminal subtype. In a pooled series of invasive breast carcinomas profiled using DNA microarrays, we identified 3,074 luminal cases, including 1,307 luminal B tumors, in which we searched for correlations between ESPL1 mRNA expression and molecular and histoclinical features. Compared to normal breast samples, ESPL1 was overexpressed in 52 % of luminal tumors, and much more frequently in luminal B (83 %) than luminal A tumors (29 %). In luminal breast cancers, higher ESPL1 expression was associated with poor-prognosis criteria (age ≤ 50 years, ductal type, advanced stage, large tumor size, lymph node-positive status, high grade, PR-negative status, luminal B subtype) and with poor metastasis-free survival in both uni- and multivariate analyses. This independent prognostic value was also observed in luminal B tumors only, and persisted when compared with gene expression signatures (PAM50, Recurrence Score, Mammaprint, EndoPredict) currently proposed to refine the indications of adjuvant chemotherapy in hormone receptor-positive/HER2-negative breast cancer. We also confirmed the observations made with experimental mouse models: ESPL1-overexpressing luminal tumors showed complex genomic profiles and molecular features of chromosomal instability and loss of tumor suppressor genes (P53 and Rb). Our results reinforce the idea that ESPL1 is a candidate oncogene in luminal B cancers. Its expression may help improve the prognostication. Inhibiting ESPL1 may represent a promising therapeutic approach for these poor-prognosis tumors. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/25086634/ESPL1_is_a_candidate_oncogene_of_luminal_B_breast_cancers_ L2 - https://doi.org/10.1007/s10549-014-3070-z DB - PRIME DP - Unbound Medicine ER -