University of Oulu

Isohookana, J., Haapasaari, K., Soini, Y., Leppänen, J., Karihtala, P. (2018) Proteins of the retinoblastoma pathway, FEN1 and MGMT are novel potential prognostic biomarkers in pancreatic adenocarcinoma. Pathology - Research and Practice, 214 (6), 840-847. doi:10.1016/j.prp.2018.04.016

Proteins of the retinoblastoma pathway, FEN1 and MGMT are novel potential prognostic biomarkers in pancreatic adenocarcinoma

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Author: Isohookana, Joel1; Haapasaari, Kirsi-Maria2; Soini, Ylermi2,3;
Organizations: 1Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu
2Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu
3Department of Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Cancer Center of Eastern Finland
4Department of Surgery, Medical Research Center Oulu, Oulu University Hospital and University of Oulu
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2018103039042
Language: English
Published: Elsevier, 2018
Publish Date: 2019-05-01
Description:

Abstract

Background: We studied the expression of some major proteins involved in cell-cycle regulation and DNA repair, the roles of which are not well known in pancreatic ductal adenocarcinoma (PDAC), but which have a significant impact on carcinogenesis of many other cancers.

Methods: We immunohistochemically assessed expression levels of the cell-cycle regulators Rb1, p16 and cyclin-dependent kinase 4 (CDK4), and the DNA repair enzymes O6-methylguanine-DNA-alkyltransferase (MGMT) and flap endonuclease-1 (FEN1) separately in malignant tissue and benign tissue from resection margins in 102 cases of PDAC. Nearly all (95.1%) patients had undergone pancreaticoduodenectomy.

Results: The studied proteins showed wide but somewhat variable expression in both benign and malignant pancreatic tissues. Strong CDK4 expression in islets of Langerhans predicted poor relapse-free survival (RFS) (HR 2.874; 95% CI 1.261–6.550; p = .012) and within T3–4 tumors CDK4 expression in adenocarcinoma cells also predicted poor disease-free survival (DFS) (RR 2.148; 95% CI 1.081–4.272; p = .029). Strong MGMT expression was associated in N1 patients with weak local relapse-free survival (RFS), DFS and overall survival; all significantly in Cox regression analysis. FEN1 was also an independent predictor of decreased DFS (in the whole study population) and worse RFS (in the patients with T3–4 tumors).

Conclusions: Major cell-cycle regulator also have predictive significance, but further studies are required to evaluate this.

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Series: Pathology. Research and practice
ISSN: 0344-0338
ISSN-E: 1618-0631
ISSN-L: 0344-0338
Volume: 214
Issue: 6
Pages: 840 - 847
DOI: 10.1016/j.prp.2018.04.016
OADOI: https://oadoi.org/10.1016/j.prp.2018.04.016
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3122 Cancers
Subjects:
Funding: This work was supported by grants from the Maud Kuistila Memorial Foundation, the Mary and Georg C. Ehrnrooth Foundation, the Finnish Anti-Tuberculosis Association and the Ida Montin Foundation.
Copyright information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/