A Specific Cadherin Phenotype May Characterize the Disseminating Yet Non-Metastatic Behavior of Pseudomyxoma Peritonei

R Bibi, N Pranesh, MP Saunders, Cancer Research UK Immunology Group, Paterson Institute for Cancer Research, Manchester UK.

British Journal of Cancer,2006, Vol. 95, pp. 1258-1264

Link to article

This study aims at identifying the molecular markers that may be linked to the particular pathology and behavior of PMP. Markers are molecules that are associated with certain characteristics of tumor cells. The aspects of PMP that the study seeks to investigate are: the origin of the disease, mucin production, and the characteristic containment of the disease within the abdominal cavity and absence of spread beyond it. The investigators studied the expression of four marker groups each corresponding to a stage in the development of cancer:

1- Markers of cell differentiation (when normal cells begin to change into cancerous cells). These are carcinoembryonic antigen (CEA), cytokeratins (CK20, CK7) and epithelial membrane antigen (EMA).

2- Markers of cell proliferation (when cancer cells begin to divide excessively). These are MUC-2, Interleukin-9 (IL-9) and its receptor (IL-9x)

3- Markers of mucin secretion

4- Markers of cell adhesion and invasion (the point at which cells lose their ability stick firmly to each other). These are N-cadherin and N-cadherin and vimentin.

Investigators compared these markers in PMP cells, normal colonic tissue and colorectal adenocarcinoma tissue. The most important finding was that each tissue type was associated with specific cadherin and vimentin expression. The table below shows these results:

N-cadherin

E-cadherin

Vimentin

Normal colonic tissue

Lack of expression

expressed

Lack of expression

Colorectal adenocarcinoma

Increased expression in stepwise manner with advancing stage

Reduced expression

PMP

Increased expression

Reduced expression

A third of the cells expressed it

These findings may explain that although PMP may spread aggressively within the abdominal cavity it usually does not spread beyond it. For the N-cadherin indicates that normal cells progressing to cancer cells, while the decrease in E-cadhering and increase in expression of vimentin means that the cells are loosing their ability to adhere sufficiently to become invasive and are free-floating in the abdominal cavity. Much similar to colorectal adenocarcinoma, all PMP tissues were CEA positive, and all but one were CK20 positive.

Limitations of this study:

1- Small sample size which prohibits studying particular subtypes of PMP
No account was taken of mRNA expression