Abstract
BackgroundL1 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.MethodsFormalin-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.ResultsPositive 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).ConclusionL1CAM 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.
Highlights
Cervical cancer is the fourth most common type of cancer among women worldwide [1]
L1 cell adhesion molecule (L1CAM) expression was independently associated with locoregional recurrence-free survival, 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
Summary
Cervical cancer is the fourth most common type of cancer among women worldwide [1]. Cervical cancer spreads in a progressive and predictable manner through regional lymphatics, suggesting that disease-recurrence is a result of insufficient primary treatment. Adjuvant radiotherapy after primary radical surgery is indicated when two out of three pathologic factors are present: vaso-invasion, tumor size ≥4cm, and tumor invasion ≥2/3 or ≥15mm (Sedlis criteria), but the risk of recurrences is only reduced by ~50% [2, 3]. Aside from currently used pathologic factors, molecular tumor markers might be helpful in predicting disease-recurrence, improving the selection of patients requiring adjuvant treatment. 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). We determined the prognostic significance of L1CAM in cervical cancer and its association with vimentin expression on tumor cells, indicative of EMT
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