Prognostic significance of single isolated cells with decreased E-cadherin expression in pseudomyxoma peritonei.

Abstract

Pseudomyxoma peritonei (PMP) cases can be classified into the prognosis-related subtypes of disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA). To investigate the mechanisms of mucinous invasion and the differing prognoses of these two subtypes, we examined the expression levels of proteins involved in cellular adhesion and invasion, including E-cadherin, vimentin, β-catenin, and S100A4, in single isolated tumor cells (SICs) and cohesive cellular strips within mucin pools isolated from DPAM (n = 31) and PMCA (n = 21) patients. In both PMCA and DPAM cases, SICs showed a complete loss of E-cadherin expression, whereas cells in cohesive cellular clusters retained E-cadherin expression. The frequency of high numbers of SICs (>8) in PMCA cases was significantly greater than that in DPAM cases (86% and 26%, respectively) and was correlated with poor progression-free survival (P = 0.019) in a univariate analysis. In both PMP subtypes, strong vimentin expression was identified in most of the SICs but not the cohesive cellular strips. The relatively slow progression of DPAM may be attributable to the smaller number of SICs that lack E-cadherin expression and have increased vimentin expression, whereas the rapid progression of PMCA may be due to larger numbers of these SICs.