Epithelial to Mesenchymal Transition in Peripheral Cholangiocarcinoma
N Guedj, PE Rautou, F David, B Jacques, B Pierre, F Olivier, P Valerie. Beaujon Hospital, Clichy, France
Background: Epithelial to mesenchymal transition (EMT), defined by the loss of epithelial characteristics and the acquisition of mesenchymal phenotype, has been shown to play a major role in tumoral invasion. Several morphological features of peripheral CC, such as the presence of an abundant desmoplastic stroma, frequent neural invasion and satellite nodules, suggest that EMT could be activated in these tumors. Therefore, we aimed to study expression of relevant markers consistent with the acquisition of an EMT phenotype and to evaluate the implication of this process in the aggressiveness of peripheral CC.
Design: Clinicopathological data were retrospectively collected from 57 peripheral CC surgically treated. We evaluated the expression of several EMT markers, including different types of cytokeratins (CK), vimentin and adhesion cell molecules (Ep-CAM, E-cadherin) using immunohistochemistry in tissue microarray. EMT phenotype was considered present when tumors acquired vimentin expression (>10% of tumor cells), and displayed a decreased expression in at least one CK (<20%). We also noted if an aberant E-Cadherin cytoplasmic staining was present. Main histoprognostic criteria of CC were correlated with expression of each EMT tissue marker.
Results: Mean age was 59.3±10.9 years [33-82] with 32 females and 25 males. Mean tumor size was 7.9±4.3cm [0.5-22]. Tumors corresponded to well-differentiated (n=36) or moderatly/poorly-differentiated adenocarcinomas (n=22). We observed that 24 CC (42%) expressed vimentin. We noted a decreased in CK8 expression and an aberrant E-cadherin cytoplasmic staining respectively in 19% and in 58% of tumors. According to our criteria, 16% (n=9) of peripheral CC displayed an EMT phenotype. CC with EMT phenotype did not differ from CC without EMT phenotype regarding tumor size, differentiation grade, presence of satellite nodules, perineural and node invasion. However, decreased expression of CK8 and CK19 was respectively associated with vascular invasion (63% vs 80%, p=0.06) and lymph node metastasis (86% vs 98%, p<0.0001). Decreased expression of Ep-CAM was also associated with lymph node involvement (23% vs 4%, p=0.043).
Conclusions: Our results showed that a small proportion of peripheral CC switch from epithelial to a mesenchymal phenotype but no evidence clinical relevance was observed. Nevertheless, we found that the progressive acquisition of an EMT process is implied in the invasiveness of peripheral cholangiocarcinoma.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 190, Tuesday Afternoon