MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type

Abstract

Complete surgical resection of the tumor is the sole approach to improve the cure rate of patients with intrahepatic cholangiocarcinoma-mass forming type (ICC-MF). Although patients are treated by curative resection, many of them show poor outcome. Mucin (MUC)4 expression has been implicated as a marker for diagnosis and progression of pancreatic adenocarcinomas, but there is no study of the relationship between MUC4 expression and patient's prognosis in ICC-MF. In the present study, we examined the expression profile of MUC4 in ICC-MF tissue from 27 patients using immunohistochemistry. MUC4 was expressed in the carcinoma tissues of 10 (37%) of the 27 ICC-MF tumors, whereas it was not expressed in normal liver tissue. Because MUC4 is an intramembrane ligand for receptor tyrosine kinase ErbB2 and is related with regulation of p27, we also compared the MUC4 expression with ErbB2 and p27 expressions in ICC-MFs. The patients with MUC4 and ErbB2 double positive expression showed a short survival period compared to non-expressing patients. MUC4 and p27 showed no relationship. The univariate analysis showed that tumor size, intrahepatic metastasis, lymph node metastasis, MUC4 expression, and MUC1 expression were statistically significant risk factors affecting the outcome of the patients with ICC-MF. The multivariate analysis demonstrated that MUC4 expression, as well as surgical margin, were statistically significant independent risk factors. In conclusion, the results suggest that expression of MUC4 in ICC-MF is a new independent factor for poor prognosis and is a useful marker to predict the outcome of the patients with ICC-MF. (HEPATOLOGY 2004;39:220 -229.)

The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis

“…The evidence that Muc4 potentiates HER2 signaling has led to the hypothesis that it may promote HER2 tumorigenic signaling even in tumors that do not overexpress HER2. Consistent with this hypothesis, increased expression of Muc4 is associated with worse prognosis in several types of cancer (Shibahara et al, 2004;Saitou et al, 2005;Tamada et al, 2006;Tsutsumida et al, 2006). Further analysis of this hypothesis awaits models that more definitively demonstrate the role of Muc4 in promoting tumorigenic HER2 function.…”

Prognostic molecular markers in cholangiocarcinoma: A systematic review

“…In CC, however, four groups have examined HER-2/neu expression using IHC and found no correlation with survival (61,62,74,75).…”

“…Of the nine studies that have examined the prognostic value of MUC1 in CC, all except one have demonstrated a significant correlation between MUC1 expression and decreased survival, both on univariate and multivariate survival analyses (61,62,(101)(102)(103)(104)(105)(106)(107).…”

“…High expression has been shown by two groups to significantly correlate with poor survival and act as an independent prognostic factor on multivariate analysis (61,62).…”

Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas

“…Immunohistochemistry for the detection of alpha-fetoprotein, alpha-1-antitrypsin, different types of cytokeratins (CKs), hepatocyte-specific antigen (HSA) and other markers-as syndecan-1, tenascin, mucin 1 and 4, b-catenin alteration-might help in establishing the correct diagnosis or to determine the prognosis. [5][6][7][8][9][10] Tight junctions, the most apical part of the intercellular junctional complex, play an essential role in maintaining cell polarity and determining paracellular permeability in organs of epithelial origin. 11,12 Cell adhesion, polarity and intercellular communication are especially important in the trabecular structure of the liver and in the formation of the bile duct system, where tight junctions separate bile flow from plasma.…”