Endometrial cancer prognosis correlates with the expression of L1CAM and miR34a biomarkers

Abstract

Background: Patients with endometrial cancer (EC) and presumably with good prognosis may develop a recurrence indicating that the classification of this tumor is still not definitive and that new markers are needed to identify a subgroup at risk of relapse. The cell adhesion molecule L1CAM is highly expressed in several human carcinomas and has recently been described as a new marker for endometrial and ovarian carcinomas. The aim of this study was to determine the relevance of L1CAM in recurrent EC.

Methods: In this work we have analyzed, by immunohistochemical and RT-qPCR analysis, the expression of L1CAM in a cohort of 113 endometrial cancers at different stages, which 50% have relapsed. As a predictor of good outcome, the tumors were also analyzed for the expression of miR-34a, a post-transcriptional regulator of L1CAM.

Results: Among metastatic EC, the highest levels (60%) and the median level (24%) of L1CAM in tumors correlate with the progression, suggesting that the expression of this molecule is linked to the tumor component most involved in metastatic processes. We also found an inverse correlation between miR-34a and L1CAM protein expression, suggesting that miR-34a is a positive prognostic marker of EC.

Conclusions: Our results demonstrate the expression of L1CAM and miR-34a in EC as prognostic factors that identify subgroup of patients at high risk of recurrence suggesting for them more aggressive schedules of treatment.

Keywords: Endometrial cancer; Innovative biotechnology; L1CAM; Personalised approach; Prognostic biomarker.

Fig. 1

Representative immunohistochemical staining of L1CAM in recurrent and non-recurrent EC. FFPE tumor tissues derived from recurrent EC displaying a strong (score 3+) (a) and a moderate (score 2+) (b) L1CAM positivity, respectively. FFPE tumor tissues derived from no recurrence EC displaying a mild focal positivity (score 2+ in the 20% of tumor cells) (c) and no L1CAM immune-reactivity (d). Scale bar 50 μm

Fig. 2

The DFS according to L1CAM expression and age of patients. Kaplan-Meier estimate DFS for (a) L1CAM expression (≤20% vs >  20% of positive cells, respectively) (P = 0.002), and (b) age of the patients (≤67 vs > 67) (P = 0.05)

Fig. 3

The graph is representing DFS of L1CAM expression in patients of different age and tumor grade. a-b Kaplan-Meier estimates DFS for L1CAM expression stratified for age of the patients (age ≤ 67 years and age > 67 years). c-d Kaplan-Meier estimate DFS for high vs low L1CAM expression stratified for grading (grading 1/2 and grading 3). P-values were calculated using the log-rank test

Fig. 4

DFS of L1CAM expression in patients of different tumor stage and histology. a-b Kaplan-Meier estimate DFS for high vs low L1CAM expression stratified in combination with type of tumors (≤IB and > IB) (P = 0.006 vs p = 0.14); and (c-d) histotype (ADK vs other) (P = 0.01 vs p = 0.25)

Fig. 5

L1CAM expression at the mRNA level on the cohort of 113 EC patients. Expression of L1CAM mRNA was examined by qRT-PCR on specimens derived from patients with no recurrence vs recurrent EC tumors (P = 0.01)

Fig. 6

DFS according to L1CAM mRNA and protein expression in EC specimens. The box plot represents the distribution of miR-34a in the two subgroups of patients. a Kaplan-Meier estimate DFS for the expression of low vs high L1CAM mRNA level (P = 0.01). b Kaplan-Meier estimate DFS for the expression of mRNA H/L1CAM L vs mRNA L/L1CAM H (P = 0.0003). c In the Box Plot are reported the miR-34a values in the two subgroups of patients (mRNA L/L1CAM H and mRNA H/L1CAM L) (P = 0.01)