title: A specific cadherin phenotype may characterise the disseminating yet non-metastatic behaviour of pseudomyxoma peritonei.
abstract: Pseudomyxoma peritonei (PMP) is a rare neoplasm of mainly appendiceal origin, characterised by excess intra-abdominal mucin production leading to high morbidity and mortality. While histological features are frequently indolent, this tumour disseminates aggressively throughout the abdominal cavity, yet seldom metastasises. This study determined the expression of several markers of colorectal differentiation (carcinoembryonic antigen (CEA), cytokeratins (CK20 and CK7), epithelial membrane antigen), mucin production (MUC-2, interleukin-9 (IL-9), IL-9 receptor (IL-9Ralpha)), and cell adhesion (N- and E-cadherin, vimentin) in PMP tissue (n=26) compared with expressions in normal colonic mucosa (n=19) and colorectal adenocarcinoma (n=26). Expressions of CEA and cytokeratins were similar for PMP as those in colorectal adenocarcinomas with the exception that the CK20-/CK7- pattern was rare in PMP (Fisher's exact test: P=0.001). Similarly, expressions of mucin-related proteins were comparable for adenocarcinoma and PMP, with the exception that IL-9 expression was uncommon in adenocarcinoma (P=0.009). Pseudomyxoma peritonei demonstrated a specific pattern of adhesion-related protein expressions of increased N-cadherin, reduced E-cadherin, and increased vimentin (P=0.004), a phenotype suggesting a possible epithelial-mesenchymal transition state. Primary PMP cell cultures were successfully maintained and demonstrated marker expressions similar to those seen in in vivo tissues. These early characterisation studies demonstrate similarities between PMP and colorectal adenocarcinoma, but also reveal a specific cadherin phenotype that may characterise the distinct non-metastasising behaviour of PMP, and form the basis for future mechanistic and therapy-targeting research.
authors.affiliation: Cancer Research UK Immunology Group, Paterson Institute for Cancer Research, Manchester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bibi
authors.forename: N
authors.initials: N
authors.lastname: Pranesh
authors.forename: M P
authors.initials: MP
authors.lastname: Saunders
authors.forename: M S
authors.initials: MS
authors.lastname: Wilson
authors.forename: S T
authors.initials: ST
authors.lastname: O'dwyer
authors.forename: P L
authors.initials: PL
authors.lastname: Stern
authors.forename: A G
authors.initials: AG
authors.lastname: Renehan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000032:analysis*; D002272:Carcinoembryonic Antigen / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016906:Interleukin-9 / Q000032:analysis; D053554:Keratin-20 / Q000032:analysis; D053552:Keratin-7 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000032:analysis; D055262:Mucin-2; D009077:Mucins / Q000032:analysis; D009362:Neoplasm Metastasis; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000473:pathology*; D011553:Pseudomyxoma Peritonei / Q000378:metabolism / Q000473:pathology*; D053651:Receptors, Interleukin-9 / Q000032:analysis; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000032:analysis
chemical_list: D015820:Cadherins; D002272:Carcinoembryonic Antigen; D016906:Interleukin-9; D053554:Keratin-20; D053552:Keratin-7; C524625:MUC2 protein, human; D018396:Mucin-1; D055262:Mucin-2; D009077:Mucins; D053651:Receptors, Interleukin-9; D014746:Vimentin