Validation study of MARCKSL1 as a prognostic factor in lymph node-negative breast cancer patients

Nina Gran Egeland; Marie Austdal; Bianca van Diermen-Hidle; Emma Rewcastle; Einar G Gudlaugsson; Jan P A Baak; Ivar Skaland; Emiel A M Janssen; Kristin Jonsdottir

doi:10.1371/journal.pone.0212527

Validation study of MARCKSL1 as a prognostic factor in lymph node-negative breast cancer patients

PLoS One. 2019 Mar 11;14(3):e0212527. doi: 10.1371/journal.pone.0212527. eCollection 2019.

Authors

Nina Gran Egeland^{1

2}, Marie Austdal^{1

3}, Bianca van Diermen-Hidle¹, Emma Rewcastle¹, Einar G Gudlaugsson¹, Jan P A Baak^{1

4}, Ivar Skaland¹, Emiel A M Janssen^{1

2}, Kristin Jonsdottir¹

Affiliations

¹ Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
² Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.
³ Department of Breast and Endocrine Surgery, Stavanger University Hospital, Stavanger, Norway.
⁴ Dr. Med. Jan Baak AS, Tananger, Norway.

Abstract

Protein expression of Myristoylated alanine-rich C kinase substrate like-1 (MARCKSL1) has been identified as a prognostic factor in lymph-node negative (LN-) breast cancer patients. We aim to validate MARCKSL1 protein expression as a prognostic marker for distant metastasis-free survival (DMFS) in a new cohort of LN- breast cancer patients. MARCKSL1 expression was evaluated in 151 operable T1,2N0M0 LN- breast cancer patients by immunohistochemistry. Median follow-up time was 152 months, range 11-189 months. Results were compared with classical prognosticators (age, tumor diameter, grade, estrogen receptor, and proliferation) using single (Kaplan-Meier) and multivariate (Cox model) survival analysis. Thirteen patients (9%) developed distant metastases. With both single and multiple analysis of all features, MARCKSL1 did not show a significant prognostic value for DMFS (p = 0.498). Of the assessed classical prognosticators, only tumor diameter showed prognostic value (hazard ratio 9.3, 95% confidence interval 2.8-31.0, p <0.001). MARCKSL1 expression could not be confirmed as a prognostic factor in this cohort. Possible reasons include changes in diagnostic and treatment guidelines between the discovery and validation cohorts. Further studies are needed to reveal the potential biological role of this protein in breast cancer.

Publication types

Clinical Trial
Multicenter Study
Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Adult
Aged
Biomarkers, Tumor / metabolism*
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism*
Breast Neoplasms / mortality*
Breast Neoplasms / pathology
Calmodulin-Binding Proteins
Disease-Free Survival
Female
Follow-Up Studies
Humans
Lymph Nodes
Membrane Proteins / metabolism*
Microfilament Proteins
Middle Aged
Neoplasm Proteins / metabolism*
Survival Rate

Substances

Biomarkers, Tumor
Calmodulin-Binding Proteins
MARCKSL1 protein, human
Membrane Proteins
Microfilament Proteins
Neoplasm Proteins

Grants and funding

KJ (2013) and NGE (2014) were financed by the Folke Hermansen Foundation (http://www.folke-fondet.org/). The Pathology Research Foundation of the Department of Pathology (SUH) contributed to the immunohistochemical stainings. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.