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Prognostic significance of single isolated cells with decreased E-cadherin expression in pseudomyxoma peritonei
Young Wha Koh1, Sun-Young Jun, Kyu-Rae Kim
1Department of Pathology, Ajou University School of Medicine, Suwon, South Korea.
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.
Insights
Pseudomyxoma peritonei (PMP) subtypes, DPAM and PMCA, differ in prognosis due to single isolated tumor cells (SICs). PMCA has more SICs lacking E-cadherin and expressing vimentin, leading to faster progression.
Area of Science:
- Oncology
- Gastroenterology
- Pathology
Background:
- Pseudomyxoma peritonei (PMP) encompasses two subtypes: disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA).
- These subtypes exhibit distinct prognoses, suggesting underlying differences in tumor cell behavior and invasion mechanisms.
Purpose of the Study:
- To investigate the molecular mechanisms driving mucinous invasion in PMP.
- To elucidate the differing prognoses between DPAM and PMCA by examining cellular adhesion and invasion protein expression.
Main Methods:
- Analysis of E-cadherin, vimentin, β-catenin, and S100A4 protein expression in single isolated tumor cells (SICs) and cohesive cellular strips.
- Tumor samples were isolated from DPAM (n=31) and PMCA (n=21) patients.
Main Results:
- Single isolated tumor cells (SICs) in both PMP subtypes demonstrated a complete loss of E-cadherin expression, unlike cohesive cellular clusters.
- PMCA cases showed a significantly higher frequency of SICs (>8) compared to DPAM cases (86% vs. 26%).
- High SIC numbers in PMCA correlated with poorer progression-free survival (P=0.019).
- Vimentin expression was strong in SICs but absent in cohesive cellular strips across both subtypes.
Conclusions:
- The reduced number of E-cadherin-negative, vimentin-expressing SICs in DPAM may contribute to its slower progression.
- The increased prevalence of these SICs in PMCA likely drives its more aggressive clinical course and poorer prognosis.
