The CIN4 chromosomal instability qPCR classifier defines tumor aneuploidy and stratifies outcome in grade 2 breast cancer.

Attila Marcell Szász, Qiyuan Li, Aron Charles Eklund, Zsófia Sztupinszki, Andrew Rowan, Anna-Mária Tőkés, Borbála Székely, András Kiss, Miklós Szendrői, Balázs Győrffy, Zoltan Imre Szallasi, Charles Swanton, Janina Kulka

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    Abstract

    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 69.468.2 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.
    Original languageEnglish
    JournalPloS one.
    Volume8
    Issue number2
    Pages (from-to)e56707
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2013

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