The CIN4 Chromosomal Instability qPCR Classifier Defines Tumor Aneuploidy and Stratifies Outcome in Grade 2 Breast Cancer

Culhane, Aedín C. and Szász, Attila Marcell and Li, Qiyuan and Eklund, Aron C. and Sztupinszki, Zsófia and Rowan, Andrew and Tőkés, Anna-Mária and Székely, Borbála and Kiss, András and Szendrői, Miklós and Győrffy, Balázs and Szállási, Zoltán and Swanton, Charles and Kulka, Janina (2013) The CIN4 Chromosomal Instability qPCR Classifier Defines Tumor Aneuploidy and Stratifies Outcome in Grade 2 Breast Cancer. PLoS ONE, 8 (2). e56707. ISSN 1932-6203


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Purpose: Quantifying chromosomal instability (CIN) has both prognostic and predictive clinical utility in breast cancer. In order to establish a robust and clinically applicable gene expression-based measure of CIN, we assessed the ability of four qPCR quantified genes selected from the 70-gene Chromosomal Instability (CIN70) expression signature to stratify outcome in patients with grade 2 breast cancer. Methods: AURKA, FOXM1, TOP2A and TPX2 (CIN4), were selected from the CIN70 signature due to their high level of correlation with histological grade and mean CIN70 signature expression in silico. We assessed the ability of CIN4 to stratify outcome in an independent cohort of patients diagnosed between 1999 and 2002. 185 formalin-fixed, paraffin-embedded (FFPE) samples were included in the qPCR measurement of CIN4 expression. In parallel, ploidy status of tumors was assessed by flow cytometry. We investigated whether the categorical CIN4 score derived from the CIN4 signature was correlated with recurrence-free survival (RFS) and ploidy status in this cohort. Results: We observed a significant association of tumor proliferation, defined by Ki67 and mitotic index (MI), with both CIN4 expression and aneuploidy. The CIN4 score stratified grade 2 carcinomas into good and poor prognostic cohorts (mean RFS: 83.864.9 and 69.4 +- 8.2 months, respectively, p = 0.016) and its predictive power was confirmed by multivariate analysis outperforming MI and Ki67 expression. Conclusions: The first clinically applicable qPCR derived measure of tumor aneuploidy from FFPE tissue, stratifies grade 2 tumors into good and poor prognosis groups.

Item Type: Article
Subjects: R Medicine / orvostudomány > RB Pathology / patológia, kórtan
Depositing User: Elvira Rigóné Kálé
Date Deposited: 05 Feb 2014 18:02
Last Modified: 05 Feb 2014 18:02

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