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  • Review Article
  • Published:

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

Nature Reviews Clinical Oncology volume 13, pages 291–304 (2016)Cite this article

Subjects

This article has been updated

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

Abstract

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.

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Figure 1: Assessment of DNA-ploidy status by DNA cytometry.

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Change history

  • 02 December 2015

    In the version of this Review originally posted online, the VICTOR trial was inaccurately referred to as the VITOR trial in one instance. This error has now been corrected in the print and online versions of the article.

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Authors and Affiliations

  1. Institute for Cancer Genetics and Informatics, Norwegian Radium Hospital, Oslo University Hospital, Ullernchausseen 70, Oslo, 0379, Norway

    Håvard E. Danielsen & Manohar Pradhan

  2. Department of Histopathology, University College Hospitals NHS Foundation Trust, 235 Euston Road, London, NW1 2BU, UK

    Marco Novelli

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  1. Håvard E. Danielsen
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All authors contributed substantially to researching data, discussion of content, writing, and review/editing of the manuscript.

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Correspondence to Håvard E. Danielsen.

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Competing interests

M.N. is a Medical Director at Room4 Ltd, a UK company that develops and sells ploidy systems. The other authors declare no competing interests.

Supplementary information

Supplementary Figure 1

DNA ploidy histograms generated for formalin-fixed paraffin-embedded tissues from a diploid tumour and an aneuploid tumour using FCM and ICM (DOCX 152 kb)

Supplementary Table 1

The prognostic importance of ploidy in patients with invasive breast cancer (DOCX 77 kb)

Supplementary Table 2

The prognostic importance of ploidy in patients with endometrioid endometrial cancer (DOCX 70 kb)

Supplementary Table 3

The prognostic importance of ploidy in patients with early stage ovarian cancer, including BOT (DOCX 74 kb)

Supplementary Table 4

Aneuploidy and cancer of uterine cervix (DOCX 47 kb)

Supplementary Table 5

Aneuploidy and colorectal cancer arising in patients with colitis and Crohn disease (DOCX 44 kb)

Supplementary Table 6

The prognostic importance of ploidy in colorectal cancer (DOCX 97 kb)

Supplementary Table 7

Prognosis studies with ploidy measured in pre-surgical needle or transurethral biopsy specimens from patients with prostate cancer (DOCX 67 kb)

Supplementary Table 8

Prognosis studies with ploidy measured in radical prostatectomy specimens from patients with prostate cancer (DOCX 30 kb)

Supplementary Table 9

Aneuploidy and prognosis in patients with bladder carcinoma (DOCX 22 kb)

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Danielsen, H., Pradhan, M. & Novelli, M. Revisiting tumour aneuploidy — the place of ploidy assessment in the molecular era. Nat Rev Clin Oncol 13, 291–304 (2016). https://doi.org/10.1038/nrclinonc.2015.208

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