Clinicopathologic Characteristics and Neoplasia Risk of Colorectal Inflammatory Polyposis in Inflammatory Bowel Disease.

CONTEXT.­: Inflammatory polyps (IPs) in inflammatory bowel disease may have been associated in the past with increased neoplasia risk. Additionally, colonic mucosa in filiform polyposis and giant inflammatory polyposis may be difficult to visualize during endoscopic surveillance, perhaps contributing to early colectomy in these patients. OBJECTIVE.­: To examine the clinicopathologic characteristics and significance of IPs and inflammatory polyposis in inflammatory bowel disease. DESIGN.­: We identified 336 resections from inflammatory bowel disease patients (212 [63.1%] male; mean age, 40.3 years; 175 [52.1%] with ulcerative colitis), including 78 with rare/few (<10) IPs, 141 with multiple (≥10) IPs, and 117 with inflammatory polyposis (including 30 with filiform polyposis/giant inflammatory polyposis) and compared them with 100 controls without IPs along various parameters, including overall and occult (unexpected) dysplasia. RESULTS.­: There was no increased neoplasia in resections with IPs compared with controls, given similar age, disease duration, degree of inflammation, anatomical extent of colitis, prevalence of primary sclerosing cholangitis, and tissue sampling. Increasing numbers of IPs and inflammatory polyposis were significantly associated in multivariate analysis with ulcerative and indeterminate colitis (P = .003) and shorter disease duration (P = .01), but also, and independently, with lower rates of dysplasia overall, including all grades (P = .001) and advanced neoplasia (P = .04). There were no instances of occult dysplasia (any grade) among inflammatory polyposis cases. CONCLUSIONS.­: These findings support the conclusion that the presence of IPs per se, and inflammatory polyposis in particular (including filiform polyposis and giant inflammatory polyposis), should not be considered an independent risk factor for the development of neoplasia in inflammatory bowel disease patients, outside the context of disease duration and inflammatory burden.

Reduced E-Cadherin and Aberrant ß-Catenin Expression are Associated With Advanced Disease in Signet-Ring Cell Carcinomas.

Signet-ring cell carcinomas (SRCCs) tend to present at higher stages and thus are generally associated with a worse prognosis. It has been postulated that a deficiency of E-cadherin may be causal in the pathogenesis of SRCC in animal models. In this study, we systemically analyzed the expression of E-cadherin and ß-catenin, a key component of the cadherin complex, in 137 consecutive SRCCs of various organ systems to explore the significance of these molecules in the pathogenesis and progression of SRCCs. Seventy-six percent of SRCCs showed loss or reduced E-cadherin expression. Aberrant ß-catenin expression, defined as loss of membranous expression and nuclear/cytoplasmic subcellular localization, was observed in 60% of these cases, with the altered ß-catenin expression observed most commonly in the breast (93%) and least in the lung (38%) primaries. Further, the aberrant ß-catenin was significantly associated with pathologic nodal stage (P=0.002) and clinical stage (P=0.02). Our findings demonstrated that reduced membranous E-cadherin and aberrant ß-catenin expression were frequent events in SRCCs of various organs, and that the altered ß-catenin expression was significantly associated with advanced disease. The observations further support the importance of these molecules in the pathogenesis of SRCCs, and indicate the fundamental role of the Wnt/ß-catenin signaling pathway in the progression of these tumors. Further investigations of the downstream molecules in this cascade may provide potential novel therapeutic targets for this aggressive tumor type.

Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell carcinoma of the upper gastrointestinal system: a potential anchor for metastatic deposition.

AIMS: To examine the expression of E-cadherin in paired primary and metastatic signet-ring cell carcinomas (SRCC) of various organ systems in order to explore the potential role of the molecule in metastatic dissemination of this unique tumour type. METHODS: Thirty-seven consecutive cases of SRCC from various organs with paired primary and metastatic tumorous tissue available were retrieved. The intensity of membranous E-cadherin expression was semiquantitatively scored on a scale of 0-3+. RESULTS: Reduced E-cadherin expression was a distinct feature of primary SRCC and was observed in 78% of primary tumours. Interestingly, the E-cadherin reduction was less frequently seen in metastatic SRCC when compared with their primary counterparts, and was only found in 57% of tumours in lymph node metastases or at distant sites of relapse. Furthermore, the mean score of E-cadherin expression of primary SRCC was significantly lower than that of their metastatic counterparts (2.3 vs 1.8; p=0.008). When divided by organ systems, the reacquisition of E-cadherin expression in the metastatic deposits was most remarkable in the SRCC of upper gastrointestinal tract origin (2.3 vs 1.4; p=0.003), whereas no significant difference was observed in other organ systems. CONCLUSIONS: While the reduction of E-cadherin in primary SRCC supports its pivotal role in epithelial-mesenchymal transition, a process crucial in tumour progression and metastatic dissemination, the re-expression of this molecule in metastatic SRCC cells implies a reversal to their epithelial phenotype (thus mesenchymal-epithelial transition) which, in turn, theoretically helps tumour cells to anchor and form cohesive metastatic deposits.