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-9Ra)), and cell adhesion (N-and E-cadherin, vimentin) in PMP tissue (n ¼ 26) compared with expressions in normal colonic mucosa (n ¼ 19) and colorectal adenocarcinoma (n ¼ 26). Expressions of CEA and cytokeratins were similar for PMP as those in colorectal adenocarcinomas with the exception that the CK20À/CK7À pattern was rare in PMP (Fisher's exact test: P ¼ 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 ¼ 0.009). Pseudomyxoma peritonei demonstrated a specific pattern of adhesion-related protein expressions of increased N-cadherin, reduced E-cadherin, and increased vimentin (P ¼ 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.

Exploring the peritoneal surface malignancy phenotype—a pilot immunohistochemical study of human pseudomyxoma peritonei and derived animal models

“…Interestingly, 2 of the models expressed CK7 in 50% to 100% of tumor cells in all sections, one concomitantly with CK20 (PMP-2), whereas one was completely negative for CK20 (PMCA-1). The results are in agreement with previously published findings that demonstrate that although CK20 is expressed in most mucinous intraabdominal malignancies of intestinal origin, it is not obligatory, and coexpression or isolated expression of CK7 is found in a subset of tumors [7,11,12]. The mesenchymal marker vimentin was not expressed in any of the sections, which is to be expected because these tumors are of epithelial origin.…”

“…As would be expected for these epithelialderived tumors, N-cadherin was generally not expressed or exhibited very slight staining. Our findings are somewhat in contrast to results from a previous study of 26 PMP samples, in which E-cadherin was expressed at lower and N-cadherin at higher levels than in simultaneously analyzed CRC samples and normal colon [11]. To determine the relevance of cadherins in PMP and mucinous PC, the expression of these molecules should be studied in larger clinical panels.…”

Technical aspects of cytoreductive surgery

“…Finally, widespread cancer dissemination (WCD) characterizes the invasive mucinous tumor that produces high quantities of mucus, which in itself interferes with cell adherence [6]. Recent evaluation of adhesion molecules in PMP and colorectal cancer has demonstrated a distinct profile that helps to explain the pattern and distribution of disease and offers potential for molecular targeting to prevent invasion [7]. The patterns of spread of the common histotypes of peritoneal carcinomatosis are described in the Table I.…”

A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pseudomyxoma peritonei

“…This regimen has yet to be systematically tested and will have to address additional practical issues, such as the requirement for central venous access and cumulative toxicity such as parasthesia. Although the understanding of the basic biology of PMP is still in its infancy (Bibi et al, 2006), for the immediate future, systemic antitumour approaches in the treatment of advanced unresectable disease will probably emerge from existing strategies for related gastrointestinal malignancies.…”