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. 2017 Nov 15;12(11):e0188068.
doi: 10.1371/journal.pone.0188068. eCollection 2017.

Prognostic significance of cyclin D1 protein expression and gene amplification in invasive breast carcinoma

Angela B Ortiz  1 , Diego Garcia  1 , Yolanda Vicente  1 , Magda Palka  2 , Carmen Bellas  1   3 , Paloma Martin  1   3
Affiliations

Prognostic significance of cyclin D1 protein expression and gene amplification in invasive breast carcinoma

Angela B Ortiz et al. PLoS One. .

Abstract

The oncogenic capacity of cyclin D1 has long been established in breast cancer. CCND1 amplification has been identified in a subset of patients with poor prognosis, but there are conflicting data regarding the predictive value of cyclin D1 protein overexpression. This study was designed to analyze the expression of cyclin D1 and its correlation with CCND1 amplification and their prognostic implications in invasive breast cancer. By using the tissue microarray technique, we performed an immunohistochemical study of ER, PR, HER2, p53, cyclin D1, Ki67 and p16 in 179 invasive breast carcinoma cases. The FISH method was performed to detect HER2/Neu and CCND1 amplification. High cyclin D1 expression was identified in 94/179 (52%) of invasive breast cancers. Cyclin D1 overexpression and CCND1 amplification were significantly associated (p = 0.010). Overexpression of cyclin D1 correlated with ER expression, PR expression and Luminal subtypes (p<0.001), with a favorable impact on overall survival in the whole series. However, in the Luminal A group, high expression of cyclin D1 correlated with shorter disease-free survival, suggesting that the prognostic role of cyclin D1 depends on the molecular subtype. CCND1 gene amplification was detected in 17 cases (9%) and correlated significantly with high tumor grade (p = 0.038), high Ki-67 protein expression (p = 0.002), and the Luminal B subtype (p = 0.002). Patients with tumors with high amplification of CCND1 had an increased risk of recurrence (HR = 2.5; 95% CI, 1.2-4.9, p = 0.01). These findings suggest that CCND1 amplification could be useful for predicting recurrence in invasive breast cancer.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Immunohistochemistry staining for cyclin D1 and CCND1 amplification (FISH) in invasive ductal breast carcinoma.
Examples of cyclin D1 expression: B-C strong nuclear staining in >50% of cells. F-G nuclear and cytoplasmic staining in most nuclei of invasive breast carcinoma. CCND1 gene amplification was evaluated by FISH. D- Clusters of CCND1 amplification, H- Low-level CCND1 amplification.
Fig 2
Fig 2. Kaplan-Meier survival analysis revealed that the expression of cyclin D1was predictive for overall survival (OS) but not disease-free survival (DFS).
CCND1 amplification was predictive for DFS. High cyclin D1 expression affected DFS in Luminal A cases.
See this image and copyright information in PMC

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