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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2012

Open Access 01-07-2012 | Translational Research and Biomarkers

Cell Cycle Proteins Predict Recurrence in Stage II and III Colon Cancer

Authors: Eric J. Th. Belt, MD, PhD, Rebecca P. M. Brosens, MD, PhD, Pien M. Delis-van Diemen, MS, Herman Bril, MD, PhD, Marianne Tijssen, MS, Dirk F. van Essen, MS, Martijn W. Heymans, PhD, Jeroen A. M. Beliën, PhD, Hein B. A. C. Stockmann, MD, PhD, Sybren Meijer, MD, PhD, Gerrit A. Meijer, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2012

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Abstract

Purpose

To investigate the prognostic value of multiple cell cycle-associated proteins in a large series of stage II and III colon cancers.

Methods

From formalin-fixed, paraffin-embedded tumor samples of 386 patients with stage II and III colon cancer, DNA was isolated and tissue microarrays were constructed. Tissue microarray slides were immunohistochemically stained for p21, p27, p53, epidermal growth factor receptor, Her2/Neu, β-catenin, cyclin D1, Ki-67, thymidylate synthase, and Aurora kinase A (AURKA). Polymerase chain reaction–based microsatellite instability analysis was performed to allow for stratification of protein expression by microsatellite instability status.

Results

Overall, low p21, high p53, low cyclin D1, and high AURKA expression were significantly associated with recurrence (P = 0.01, P < 0.01, P = 0.04, and P < 0.01, respectively). In stage II patients who did not receive adjuvant chemotherapy (n = 190), significantly more recurrences were observed in case of low-p21 and high-p53-expressing tumors (P < 0.01 and P = 0.03, respectively). In stage III patients who did not receive chemotherapy, high p53 expression was associated with recurrence (P = 0.02), and in patients who received chemotherapy, high AURKA expression was associated with relapse (P < 0.01). In patients with microsatellite stable tumors, high levels of p53 and AURKA were associated with recurrence (P = 0.01 and P < 0.01, respectively). Multivariate analysis showed p21 (odds ratio 1.6, 95% confidence interval 0.9–2.8) and AURKA (odds ratio 2.7, 95% confidence interval 1.3–5.6) to be independently associated with disease recurrence.

Conclusions

p21, p53, cyclin D1, and AURKA could possibly be used as prognostic markers to identify colon cancer patients with high risk of disease recurrence.
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Metadata
Title
Cell Cycle Proteins Predict Recurrence in Stage II and III Colon Cancer
Authors
Eric J. Th. Belt, MD, PhD
Rebecca P. M. Brosens, MD, PhD
Pien M. Delis-van Diemen, MS
Herman Bril, MD, PhD
Marianne Tijssen, MS
Dirk F. van Essen, MS
Martijn W. Heymans, PhD
Jeroen A. M. Beliën, PhD
Hein B. A. C. Stockmann, MD, PhD
Sybren Meijer, MD, PhD
Gerrit A. Meijer, MD, PhD
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2216-7

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