Prognostic roles of L1-cell adhesion molecule up-regulation in association with p53 overexpression and E-cadherin down-regulation in endometrial carcinoma patients

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Abstract

Background

The recent guidelines for endometrial carcinoma (EC) management classify patients into low-risk, intermediate-risk, high-to-intermediate risk, and high-risk groups. A few patients in the category of low-risk disease have been found to have relapse of the tumor; this has not been explained to date. Moreover, it is essential to assess the prognosis of other risk groups of EC. Also, the identification of patients for whom the adjuvant therapy will be more beneficial than other patients who will not require additional management after surgery is an essential aim of the recent researches on EC. Thus, recent studies have focused on the detection of prognostic biomarkers that might improve risk stratification and identify which patients will need neoadjuvant chemotherapy after surgery. L1-cell adhesion molecule (L1CAM) is a membrane glycoprotein member of the immunoglobulin superfamily. P53 is a nuclear transcription factor and was found to be an established tumor suppressor. E-cadherin is an integral cell adhesion molecule and it is a component of the adherens junction.

Background

The aim of our study is to investigate the prognostic significance of L1CAM, p53, and E-cadherin expression in early-stage, low-risk, intermediate-risk, and high-risk EC, and correlate their expression with clinicopathological criteria, tumor progression, recurrence, risk stratification of EC patients, and identification of patients who will require neoadjuvant chemotherapy after surgery.

Patients and methods

Expressions of L1CAM, p53, and E-cadherin were evaluated in 60 paraffin blocks of EC patients who were followed up for 5 years. The relationship between their level of expressions, clinicopathological criteria, and the prognosis of the patients was analyzed.

Results

A positive expression of L1CAM was correlated positively with the presence of nonendometroid endometrial carcinoma (NEEC) (P=0.36), higher grade of the tumor (P=0.043), presence of lymph node (LN) metastases (P=0.039), lymphovascular space (LVSI) (P=0.022), parametrial invasion (P=0.011), higher risk groups (P=0.021), and presence of distant metastases (P=0.039). High expression of p53 was correlated positively with the presence of NEEC, higher grade and advanced International-Federation-of-Gynecology-and-Obstetrics stage of the tumor, presence of LN metastases, LVSI, higher risk groups, and presence of distant metastases (P<0.001). A positive expression of E-cadherin was correlated negatively with the presence of NEEC (P=0.023), higher grade of the tumor (P=0.019), presence of LN metastases (P=0.010), presence of LVSI (P=0.018), higher risk groups (P=0.009), and presence of distant metastases (P=0.013). In multivariant analysis, L1CAM expression is the most significant indicator of poor disease-free survival and overall survival rates (P<0.001).

Results

We found a direct relationship between L1CAM and p53, an inverse relationship between L1CAM and E-cadherin, and an inverse relationship between p53 and E-cadherin (P<0.001).

Conclusion

L1CAM and p53 overexpression in addition to loss of E-cadherin expression in EC are associated with the nonendometrioid subtype of EC, worse clinicopathological parameters, and poor prognosis, and could enable identification of patients who may require neoadjuvant chemotherapy after surgery.

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