Oncotarget

Research Papers:

L1 cell adhesion molecule (L1CAM) is a strong predictor for locoregional recurrences in cervical cancer

Marlies Schrevel, Willem E. Corver, Margit E. Vegter, Natalja T. Ter Haar, Enno J. Dreef, Jogchum J. Beltman, Gemma Kenter, Tjalling Bosse, Cornelis D. de Kroon and Ekaterina S. Jordanova _

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Oncotarget. 2017; 8:87568-87581. https://doi.org/10.18632/oncotarget.20976

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Abstract

Marlies Schrevel1,2, Willem E. Corver1, Margit E. Vegter1, Natalja T. Ter Haar1, Enno J. Dreef1, Jogchum J. Beltman2, Gemma Kenter3, Tjalling Bosse1, Cornelis D. de Kroon2 and Ekaterina S. Jordanova1,3

1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

2Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands

3Department of Gynecology, VUmc, Centre for Gynecologic Oncology, Amsterdam, The Netherlands

Correspondence to:

Ekaterina S. Jordanova, email: [email protected]

Keywords: cervical cancer, epithelial mesenchymal transition (EMT), L1 cell adhesion molecule (L1CAM), locoregional recurrence, prognosis

Received: April 08, 2017    Accepted: August 21, 2017    Published: September 18, 2017

ABSTRACT

Background: L1 cell adhesion molecule (L1CAM) has been shown to be a prognostic marker in various cancer types, and has been suggested to play a role in epithelial mesenchymal transition (EMT). Here, we determined the prognostic significance of L1CAM in cervical cancer and its association with vimentin expression on tumor cells, indicative of EMT.

Methods: Formalin-fixed, paraffin-embedded primary tumor samples from 372 cervical cancer patients were collected for immunohistochemical analysis of L1CAM expression. In 109 FFPE specimens, the percentage of vimentin expressing tumor cells was determined by flow cytometry.

Results: Positive L1CAM expression (≥10% of tumor cells) was associated with disease-free survival, validated using RNAseq TCGA data. L1CAM expression was independently associated with locoregional recurrence-free survival (hazard ratio 2.62, 95% CI 1.33 – 5.17, P = 0.006), and strongly associated with percentage of vimentin expressing tumor cells (P = 0.003). Expression of both L1CAM and vimentin indicated a subgroup with the highest risk of recurrence (hazard ratio 3.15, 95% CI 1.25 – 7.92, P = 0.015).

Conclusion: L1CAM might be a promising new prognostic marker for locoregional recurrences in cervical cancer, and its association with vimentin expression suggests that L1CAM might affect tumor aggressiveness, possibly through EMT.


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