Journal Article

Revisiting tumour aneuploidy — the place of ploidy assessment in the molecular era

Pradhan, Manohar, Danielsen, Håvard E., Novelli, Marco

2016

Overview

Key Points Academic interest in the role of chromosomal instability (CIN) in cancer development and the influence of the resultant large-scale genomic alterations on clinical outcomes is increasing Aneuploidy — that is, the presence of an abnormal amount of cellular DNA, is an inevitable result of CIN, and this characteristic can be detected and quantified using DNA cytometry DNA ploidy (cellular DNA quantity) is an independent prognostic marker in patients with node-negative invasive breast, early stage endometrioid endometrial, early stage ovarian, prostate, or colorectal cancers In patients with Barrett oesophagus, DNA ploidy can be combined with other biomarkers to identify disease that will progress to high-grade dysplasia and/or carcinoma, and to improve the diagnostic sensitivity of pulmonary cytology In cervical screening tests, detection of aneuploid cells in Pap smears or using liquid-based cytology is a reliable, cost-effective indicator of the early stages of neoplastic progression toward squamous-cell carcinoma Chromosome instability (CIN) is gaining increasing interest as a central process in cancer, and is indicated whenever tumour cells harbour an abnormal quantity of DNA, termed 'aneuploidy'. In this Review, the authors review the literature published since 2000 that support the hypothesis that aneuploidy is a predictor of a poor prognosis in patients with cancer, focusing on the evidence from studies of seven common epithelial cancer types that performed multivariate analyses. The implications of ploidy analysis with regard to our theoretical understanding of the role of CIN in carcinogenesis, as well as its prognostic use in the clinic, are discussed. Chromosome instability (CIN) is gaining increasing interest as a central process in cancer. CIN, either past or present, is indicated whenever tumour cells harbour an abnormal quantity of DNA, termed 'aneuploidy'. At present, the most widely used approach to detecting aneuploidy is DNA cytometry — a well-known research assay that involves staining of DNA in the nuclei of cells from a tissue sample, followed by analysis using quantitative flow cytometry or microscopic imaging. Aneuploidy in cancer tissue has been implicated as a predictor of a poor prognosis. In this Review, we have explored this hypothesis by surveying the current landscape of peer-reviewed research in which DNA cytometry has been applied in studies with disease-appropriate clinical follow up. This area of research is broad, however, and we restricted our survey to results published since 2000 relating to seven common epithelial cancers (those of the breast; endometrium, ovary, and uterine cervix; oesophagus; colon and rectum; lung; prostate; and bladder). We placed particular emphasis on results from multivariate analyses to pinpoint situations in which the prognostic value of aneuploidy as a biomarker is strong compared with that of existing indicators, such as clinical stage, histological grade, and specific molecular markers. We summarize the implications of our findings for the prognostic use of ploidy analysis in the clinic and for the theoretical understanding of the role of CIN in carcinogenesis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/499 / 692/53/2422 / 692/699/67/1857 / 692/699/67/69 / 692/700/1750 / Aneuploidy / Biomarkers, Tumor - genetics / Carcinogenesis / Chromosomal Instability / DNA, Neoplasm - genetics / Flow Cytometry - methods / Fluorimetry / Genetic aspects / Humans / Identification and classification / Medicine & Public Health / Neoplasms - diagnosis / Neoplasms - genetics / Oncology / Prognosis / review-article / Risk factors / Sensitivity and Specificity / Survival Analysis