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. 2017 Sep 18;8(50):87568-87581.
doi: 10.18632/oncotarget.20976. eCollection 2017 Oct 20.

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

Marlies Schrevel  1   2 , Willem E Corver  1 , Margit E Vegter  1 , Natalja T Ter Haar  1 , Enno J Dreef  1 , Jogchum J Beltman  2 , Gemma Kenter  3 , Tjalling Bosse  1 , Cornelis D de Kroon  2 , Ekaterina S Jordanova  1   3
Affiliations

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

Marlies Schrevel et al. Oncotarget. .

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.

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

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Conflict of interest statement

CONFLICTS OF INTEREST None

Figures

Figure 1
Figure 1. Representative examples of L1 cell adhesion molecule (L1CAM) expression in cervical carcinoma
(A) diffuse staining pattern and (B) infiltration border positivity in squamous cell carcinoma, (C) diffuse staining pattern and (D) infiltration border positivity in adenocarcinoma.
Figure 2
Figure 2
Survival curves for L1 cell adhesion molecule (L1CAM) expression and (A) locoregional recurrence-free survival in the research cohort; (B) disease-free survival in the research cohort; and (C) disease-free survival in the validation cohort (TCGA data). DFS = disease-free survival; L1CAM- = protein expression <10%; L1CAM+ = protein expression ≥10%; L1CAM low = mRNA expression below median; L1CAM high = mRNA expression above median.
Figure 3
Figure 3
Survival curves for locoregional recurrence-free survival and (A) human papillomavirus type (HPV), (B) stratification for L1CAM and HPV16 / HPV other. DFS = disease-free survival; L1CAM- = L1CAM expression <10%; L1CAM+ = L1CAM expression ≥10%; HPV other = HPV18, other HPV types and HPV negative combined.
Figure 4
Figure 4
(A+D) Representative FACS analysis of tumor samples with high (A) and low (D) fraction of vimentin positive tumor cells. The keratin negative fraction is shown in green, the keratin positive fraction (i.e. tumor fraction) is shown in red. The keratin/vimentin double-positive tumor fraction is indicated with a blue square. (B+E) Immunohistochemical staining of high (B) and low (E) vimentin expression. (C+F) Immunohistochemical staining of high (C) and low (F) L1CAM expression.
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