Microsatellite instability and DNA ploidy in colorectal cancer

Potential implications for patients undergoing systematic surveillance after resection

Authors

  • Kjetil Søreide MD, PhD,

    Corresponding author
    1. Department of General and Gastroenterological Surgery, Stavanger University Hospital, Stavanger, Norway
    2. Department of Pathology, Stavanger University Hospital, Stavanger, Norway
    3. The Gade Institute of Pathology, University of Bergen, Bergen, Norway
    • Department of Surgery, Stavanger University Hospital, PO Box 8100, N-4068 Stavanger, Norway
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    • Fax: (011) 47 5151 9919

  • Aida Slewa MSc,

    1. Department of Pathology, Stavanger University Hospital, Stavanger, Norway
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  • Pål J. Stokkeland MD,

    1. Department of Radiology, Stavanger University Hospital, Stavanger, Norway
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  • Bianca van Diermen BSc,

    1. Department of Pathology, Stavanger University Hospital, Stavanger, Norway
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  • Emiel A. M. Janssen PhD,

    1. Department of Pathology, Stavanger University Hospital, Stavanger, Norway
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  • Jon Arne Søreide MD, PhD,

    1. Department of General and Gastroenterological Surgery, Stavanger University Hospital, Stavanger, Norway
    2. Department of Surgical Sciences, University of Bergen, Bergen, Norway
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  • Jan P. A. Baak MD, PhD,

    1. Department of Pathology, Stavanger University Hospital, Stavanger, Norway
    2. The Gade Institute of Pathology, University of Bergen, Bergen, Norway
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  • Hartwig Kørner MD, PhD

    1. Department of General and Gastroenterological Surgery, Stavanger University Hospital, Stavanger, Norway
    2. Department of Surgical Sciences, University of Bergen, Bergen, Norway
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Abstract

BACKGROUND:

Appropriate stratification tools for targeted surveillance after resection for colorectal cancer (CRC) are lacking. The objective of the current study was to investigate the effect of microsatellite instability (MSI) and DNA ploidy on surveillance after surgery.

METHODS:

The authors evaluated 186 consecutive, population-based patients with stage I through III CRC who underwent surgery with curative intent and who entered a systematic surveillance program. MSI was analyzed with polymerase chain reaction for 5 known quasimonomorphic markers (BAT-26, BAT-25, NR-21, NR-24, and NR-27), and DNA ploidy was analyzed with automated cytometry. Recurrence, recurrence-free survival (RFS), and disease-specific survival (DSS) were evaluated by univariate and multivariate statistical tests.

RESULTS:

Patients with MSI (20%) were significantly younger than patients without MSI (median age, 61 years vs 67 years; P = .016). Proximal location (adjusted odds ratio [AOR], 5.4; 95% confidence interval [95% CI], 2.1-14.1 [P = .001]), large tumor size (≥5 cm: AOR, 3.5; 95% CI, 1.3–9.6 [P = .015]), and poor tumor differentiation (AOR, 6.6; 95% CI, 2–21.8 [P = .002]) were associated with MSI. MSI conveyed an increased risk for locoregional recurrence (OR, 2.9; 95% CI, 1.2–7 [P = .016]), with a trend toward a shorter time to recurrence (P = .060). Neither MSI status nor DNA ploidy predicted distant metastasis, RFS, or DSS. Lymph node status was the best predictor of distant spread (AOR, 3.9; 95% CI, 2–7.9 [P < .001]) and DSS (hazard ratio, 4.9; 95% CI, 2.6–9 [P < .001]).

CONCLUSIONS:

Patients who had microsatellite instable tumors were at increased risk for locoregional recurrence, whereas lymph node status was the best predictor of distant metastasis. Clinical surveillance and choice of modality (ie, endoscopy vs radiologic imaging) may be improved when patients are stratified according to these cancer features. Cancer 2009. © 2009 American Cancer Society.

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