MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer.

Maria Caroline Vos,Nicole Ezendam,Leon F A G Massuger,Toin H Van Kuppevelt,Eva Hollemans,Anneke A M Van Der Wurff,Dorry Boll,Hans Van Der Putten,Harry Feijen,Paul Klinkhamer,Brenda Pijlman

doi:10.1186/s13048-016-0262-7

Abstract

BackgroundTo investigate the expression of MMP-14 and CD44 as well as epithelial-to-mesenchymal transition(EMT)-like changes in ovarian cancer and to determine correlations with clinical outcome.MethodsIn 97 patients with ovarian cancer, MMP-14 and CD44 expression as determined by immunohistochemistry was investigated in relation to EMT-like changes. To determine this, immunohistochemical staining of E-cadherin and vimentin was performed.ResultsPatients with expression of both MMP-14 and CD44 in their tumors had a poor prognosis despite complete debulking. Serous histology in advanced-stage tumors (FIGO IIB-IV) correlated with CD44 (rho .286, p < 0.01). Also, CD44 correlated with percentage vimentin expression (rho .217, p < 0.05).In logistic regression analysis with complete debulking as the outcome parameter, CD44 expression was found to be significant (OR 3,571 (95 % Confidence Interval 1,112–11,468) p = 0.032), though this was not the case for MMP-14 and EMT parameters.ConclusionThe subgroup of patients with double expression of MMP-14 and CD44 had a poor prognosis despite complete debulking. Serous subtype in advanced-stage patients and CD44 expression were found to be correlated with vimentin expression, and CD44 expression was found to be significantly correlated with complete debulking. However, a significant correlation between EMT and clinical parameters was not found.

Highlights

To investigate the expression of Matrix MetalloProteinase (MMP)-14 and CD44 as well as epithelial-to-mesenchymal transition(EMT)-like changes in ovarian cancer and to determine correlations with clinical outcome
MMP-14 is expressed both in the tumor epithelium and in the stroma, whereas E-cadherin is only expressed in the tumor epithelium
The patients with double expression of MMP-14 and CD44 in their tumors had a poor prognosis despite complete debulking

Summary

Introduction

To investigate the expression of MMP-14 and CD44 as well as epithelial-to-mesenchymal transition(EMT)-like changes in ovarian cancer and to determine correlations with clinical outcome. Epithelial-to-mesenchymal transition (EMT) is an important pathophysiological process. EMT enables epithelial carcinoma cells to invade the underlying stroma. EMT occurs at the tumor’s invasive front and EMT can be recognized by its surrounding stromal reaction in conventional histopathology. In most other gynecological tumors, EMT-like changes are found [1]. The invasive front is less clearly defined than in other tumors of the female genital tract. The relationship between EMT and prognosis has not been clearly established in ovarian cancer [1]

Methods

Results

Discussion

Conclusion