Research Papers:

MACROD2 expression predicts response to 5-FU-based chemotherapy in stage III colon cancer

Evert van den Broek, Sjoerd H. den Uil, Veerle M.H. Coupé, Pien M. Delis-van Diemen, Anne S. Bolijn, Herman Bril, Hein B.A.C. Stockmann, Nicole C.T. van Grieken, Gerrit A. Meijer and Remond J.A. Fijneman _

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Oncotarget. 2018; 9:29445-29452. https://doi.org/10.18632/oncotarget.25655

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Evert van den Broek1,5, Sjoerd H. den Uil1,2, Veerle M.H. Coupé3, Pien M. Delis-van Diemen1,5, Anne S. Bolijn1,5, Herman Bril4, Hein B.A.C. Stockmann2, Nicole C.T. van Grieken1, Gerrit A. Meijer1,5 and Remond J.A. Fijneman1,5

1Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands

2Department of Surgery, Spaarne Gasthuis, Haarlem, The Netherlands

3Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

4Department of Pathology, Spaarne Gasthuis, Haarlem, The Netherlands

5Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands

Correspondence to:

Remond J.A. Fijneman, email: [email protected]

Keywords: colon cancer; disease recurrence; predictive biomarker; MACROD2; response to chemotherapy

Received: May 10, 2017    Accepted: June 01, 2018    Published: June 29, 2018


Background: Colorectal cancer (CRC) is caused by genetic aberrations. MACROD2 is commonly involved in somatic focal DNA copy number losses, in more than one-third of CRCs. In this study, we aimed to investigate the association of MACROD2 protein expression with clinical outcome in stage II and stage III colon cancer.

Methods: Tissue microarrays (TMA) containing formalin-fixed paraffin-embedded tissue cores from 386 clinically well-annotated primary stage II and III colon cancers were stained by immunohistochemistry and evaluated for MACROD2 protein expression. Disease-free survival (DFS) analysis was performed to estimate association with clinical outcome.

Results: Loss of nuclear MACROD2 protein expression in epithelial neoplastic cells of stage III microsatellite stable (MSS) colon cancers was associated with poor DFS within the subgroup of 59 patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy (p=0.005; HR=3.8, 95% CI 1.4-10.0).

Conclusion: These data indicate that low nuclear expression of MACROD2 is associated with poor prognosis of patients with stage III MSS primary colon cancer who were treated with 5-FU-based adjuvant chemotherapy.

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