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Stage-specific frequency and prognostic significance of aneuploidy in patients with sporadic colorectal cancer—a meta-analysis and current overview

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Abstract

Purpose

Aneuploidy has long been suggested as an independent prognostic marker for colorectal cancer (CRC) patients and could thus aid for individualized medicine. However, due to a large spectrum of deviating studies, expert panels do not recommend ploidy assessment. In order to clarify a potential bias of stage-specific frequency of aneuploidy, we now conducted a meta-analysis combined with a systematic review regarding aneuploidy and prognosis.

Methods

A systematic, web-based search process retrieved 1935 studies published in English between 1990 and 2011. The defined endpoint for the meta-analysis was an increase in aneuploidy frequency between early- (Dukes A, B and UICC I, II; n = 3632 samples) and late-stage (Dukes C, D and UICC III, IV; n = 3440 samples) colorectal carcinomas.

Results

Of 1935 studies initially identified, 17 image (2130 patients) and 20 (7023 patients) flow cytometric studies were analyzed in detail. The meta-analysis (7072 patients) revealed late-stage CRC to be more frequently aneuploid than early-stage CRC (odds ratio 1.51, 95 % CI 1.37–1.67; p = 0.0007). Independent of tumor stage, the overall range of aneuploidy was 39 to 81 % (median 58 %), and altogether, 21 (54.1 %) studies described a significant prognostic impact of aneuploidy for overall, disease-specific, and recurrence-free survival, respectively.

Conclusions

A substantial number of studies showed a prognostic importance of aneuploidy in CRC. Furthermore, the higher frequency of aneuploidy in late-stage CRC implies an increase in genomic instability with CRC progression, indicating aneuploidy to be also a stage-specific prognostic marker.

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Acknowledgments

Grants from the Ad Infinitum Foundation, the Werner & Clara Kreitz Foundation and the H.W. & J. Hector Foundation are gratefully acknowledged. This review was performed by the North German Tumorbank of Colorectal Cancer (ColoNet) being generously funded by the German Cancer Aid Foundation (DKH #108446) and in collaboration with the Surgical Center for Translational Oncology – Lübeck (SCTO-L).

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Section of Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 16, 23538, Lübeck, Germany

    Tilman Laubert & Jens K. Habermann

  2. Institute of Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Sandra Freitag-Wolf

  3. Devision of Molecular Oncology and Immunotherapy, Department of General Surgery, University of Rostock, Rostock, Germany

    Michael Linnebacher

  4. Department of General, Visceral and Thoracic Surgery, University Clinic Hamburg-Eppendorf, Hamburg, Germany

    Alexandra König

  5. Institute for Experimental Surgery and Central Animal Research Facility, University of Rostock, Rostock, Germany

    Brigitte Vollmar

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  1. Tilman Laubert
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  2. Sandra Freitag-Wolf
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  3. Michael Linnebacher
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  4. Alexandra König
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  6. Jens K. Habermann
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on behalf of the North German Tumorbank of Colorectal Cancer (ColoNet) consortium

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Correspondence to Jens K. Habermann.

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Laubert, T., Freitag-Wolf, S., Linnebacher, M. et al. Stage-specific frequency and prognostic significance of aneuploidy in patients with sporadic colorectal cancer—a meta-analysis and current overview. Int J Colorectal Dis 30, 1015–1028 (2015). https://doi.org/10.1007/s00384-015-2259-x

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