Mucins and NCAM (CD56) in intrahepatic cholangiocarcinogenesis

Abstract

Introduction: Cholangiocarcinoma is the second most common malignant neoplasm of the hepatobiliary system. During cholangiocarcinogenesis phenotypic changes occur in the ductal epithelium, including the expression of mucins (MUC). However, the evaluating studies of the expression of mucins in the different stages of cholangiocarcinogenesis are scarce. CD56 has also contributed in differentiating benign ductal proliferation and cholangiocarcinoma; however, its expression has not been evaluated in dysplastic epithelium of the bile duct yet. Objective: To assess immunohistochemical profile of (MUC) 1, 2, 5, 6, and CD56 in cholangiocarcinoma, pre-neoplastic and reactive lesions in the epithelium of intrahepatic bile ducts. Material and methods: Immunohistochemical expression of MUC 1, 2, 5, 6, and CD56 were studied for 11 cases of cholangiocarcinoma and 83 intrahepatic bile ducts (67 reactive and 16 dysplastic). Variables were considered significant when p < 0.05. Results: The expression of MUC1 occurred in about 90% of the cholangiocarcinomas, contrasting with the low frequency of positive cases in reactive and dysplastic bile ducts (p < 0.001). However, there was no statistically significant difference in the expression of MUC5, MUC6 and CD56 between the reactive or dysplastic lesions and cholangiocarcinoma. The anti-MUC2 antibody was negative in all cases. Conclusions: MUC1 contributed for the differential diagnosis between cholangiocarcinoma and pre-neoplastic and reactive/regenerative lesions of intrahepatic bile ducts, and it should compose the antibodies panel aiming at improvement of these differential diagnoses. In contrast, MUC2, MUC5, MUC6 and CD56 were not promising in differentiating all the phases of cholangiocarcinogenesis.

Meta-analysis of the diagnostic value of Wisteria floribunda agglutinin-sialylated mucin1 and the prognostic role of mucin1 in human cholangiocarcinoma

“…A total of 341 papers were identified, of which 148 were retrieved for full-text review. Among these 148 publications, 16 studies6 7 9 10 12–15 31 32 34–37 54 55 were eligible for the meta-analyses according to the inclusion and exclusion criteria. Nine studies7 9 10 12–15 36 37 out of 16 studies used OS as endpoint, and eight studies6 9 31 32 34 35 54 55 used the sensitivity and specificity rate as the endpoint (one study reported by Huang et al also provided the data on diagnostic value of MUC1 in tissue).…”

“…Characteristics of eligible studies and their participants were listed in tables 1, table 2 and table 3. A total of nine studies7 9 10 12–15 36 37 evaluating the prognostic value of MUC1 for resectable CCA were conducted in four countries (Korea, Japan, China and Thailand), the other seven studies6 31 32 34 35 54 55 investigating the diagnostic capability of WFA-MUC1 were undertaken in five countries (Japan, UK, Brazil, Thailand and China). Retrospective study design was applied to perform the meta-analysis of prognostic value by all selected studies.…”

“…The AUC under SROC was 0.88 (95% CI 0.85 to 0.90). Furthermore, three trials6 9 54 inculding 72 subjects with CCA and 119 benign biliary disease used the positive expression of MUC1 in tissue as a criterium to discriminate CCA from benign biliary disease. The diagnostic parameters of positive expression of MUC1 in biliary duct cancer tissue were shown in figure 2D.…”

“…Currently, a huge amount of literature reporting numerous molecular biomarkers with limited diagnostic or prognostic capability for CCA have been published. Some of the reported biomarkers have been used for guiding clinical diagnosis and treatment of CCA worldwide, such as Mucin2 to Mucin6,6–15 carbohydrate antigen 19-9 (CA19-9),16–18 interleukin-6,19 20 serum cytokeratin 19 fragments21 22 and carbohydrate antigen 125 16 23 24. Among these biomarkers, CA19-9 in serum has been the focus of related research and always been used as a biomarker for CCA.…”

Tumor marker and hepatic neoplasms

“…In this edition of JBPML, you will find a paper entitled "The mucins and NCAM (CD56) in intrahepatic colangiocarcinogênese" (1) , in which the participation of different types of mucins and some adhesion molecules (NCAM) expressed in bile ducts is discussed as differential markers between reactive and dysplastic processes (3) . In addition, a particular type of mucin, MUC1 was associated with the presence of metastases, loss of differentiation and more invasive behavior of the tumor, worse prognosis, which would be reflected in reduced survival (4) .…”