Mucin Expression in Bile Ducts Neoplasms - Systematic Review and Metaanalysis

Research Article

J Gastroenterol Liver Dis. 2016; 1(1): 1004.

Mucin Expression in Bile Ducts Neoplasms - Systematic Review and Metaanalysis

Yaron Niv*

Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, Israel

*Corresponding author: Yaron Niv, Department of Gastroenterology, Rabin Medical Center, Tel Aviv University, 39 Jabotinski Street, Petach Tikva, 4910000, Israel

Received: September 01, 2016; Accepted: November 10, 2016; Published: November 14, 2016

Abstract

Introduction: The definition of bile ducts tumours is not well-established, in particular this of mucin-producing neoplasms. Intraductal Papillary Neoplasm of the Bile Duct (IPNB) is a new term for pre neoplastic lesion leading to Cholangio Carcinoma (CC). Mucin expression may characterize this transformation and also be prognostic and predictive factor.

Aim: To compare different mucin genes expression in bile ducts lesions with normal bile duct epithelium.

Methods: English Medical literature searches were conducted for “mucin” and “bile ducts”. Meta-analysis was performed by using Comprehensive metaanaslysis software. Pooled odds ratios and 95% confidence intervals were calculated.

Results: We found 298 eligible studies. 270 studies were rejected (performed in animals, not having full text, because of language, editorials, review articles, duplications). We were left with 28 studies including 4237 patients, from 6 countries that fulfilled the inclusion criteria, published till 31.7.2016. Mucin expression was significantly higher in bile ducts lesions than in normal epithelium with OR 6.81 (95%CI 3.88 – 11.93, P < 0.001). Measure of heterogeneity was moderate, demonstrated in the included studies: Q = 231.409, df (Q) = 61, P = 0.001, I2= 73.64%. OR for mucin expression in CC and IPNB was 6.4 with 95% CI 2.5 – 16.5, P<0.001, and 6.9 with 95% CI 3.4 – 13.8, P<0.0001, respectively.

MUC1, MUC2, MUC4, and MUC5AC expression was significantly increased in bile ducts lesions.

Conclusion: According to the new classification and accumulated data on different CC type’s behaviour, mucin genes expressions may serve as important clues for prognosis and prediction of treatment success.

Keywords: Mucin; Bile ducts; Gene Expression; Cholangiocarcinoma

Novelty & Impact Statements

In the first time we performed a metaanalysis and systematic review of mucin expression in malignant and pre malignant lesions of the bile ducts. MUC1, MUC2, MUC4, and MUC5AC expression was significantly increased in bile ducts lesions.

According to the new CC type’s behaviour, mucin genes expression may serve as important clues for prognosis and prediction of treatment success.

Introduction

The definition of bile ducts tumours is not well-established, in particular this of mucin-producing neoplasms. Intraductal Papillary Neoplasm of the Bile Duct (IPNB) is a new term, equivalent to the Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN) [1]. Three phenotypes of IPNB were described: pancreatobiliary, intestinal and gastric. The expression of mucin in these lesions is different, MUC1 in pancreatobiliary IPNB, MUC2 in intestinal and MUC5AC in gastric types, respectively [2-4]. These mucins are also up-regulated when IPNB transforms into carcinoma, and their expression relates to aggressive behaviour, invasion and poorer prognosis, MUC1 in ductal adenocarcinoma and MUC5AC in mucinous carcinoma.

The terms used in many studies are different and sometimes confusing. Cholangiocarcinoma (CC) may be ductal or mucinous, infiltrating or mass-forming. Sometimes investigators separate intrahepatic and extra hepatic CC, some discuss adenocarcinoma of the papilla as a separate entity and some not.

Very few studies described mucin expression in normal bile ducts. Sasaki et al found that the biliary epithelial cells switch MUC1 apomucin expression before birth to MUC3 after birth [5]. The same group found MUC3 expression in CC and biliary epithelial dysplasia (similar to normal bile ducts), but a significant decrease of MUC1 and MUC2 expression [4]. In addition they described changes in MUC1 and MUC2 expression in the carcinogenesis process, from biliary intraepithelial neoplasia and IPNB into “tubular” adenocarcinoma (MUC1 positive and MUC2 negative), and colloid carcinoma (MUC1 negative) [6].

Thus, a systematic review and metaanalysis may possibly clarify the controversial results of observational studies and collect the knowledge about mucin expression in bile ducts lesions, trying to establish a role for different mucin expressions as prognostic markers.

Methods

Search strategy

English Medical literature searches were conducted for “mucin” and “bile ducts”. Searches were performed through July 31th 2016, using MEDLINE, PubMed, Scopus, EMBASE and CENTRAL. Search terms were: “mucin” and “bile ducts”. Hand searches of articles bibliography were also performed. Only fully published human studies in English were included (Figure 1).