Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

Abstract

the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.

Multifocal pancreatobiliary malignancies: A diagnostic and therapeutic challenge

“…The malignant forms of CC and PDAC arise from their pre-malignant counterparts; namely, biliary intraepithelial neoplasia and pancreatic intraepithelial neoplasia [5] . The molecular and phenotypical similarity between extrahepatic CCs and PDAC is likely to be related to their shared embryological origin, with both the proximal pancreatic and distal biliary ducts arising from a common endodermal structure: the ventral foregut [15] .…”

“…The 2 most common mutations implicated in the carcinogenesis of PDAC (p53 and KRAS) have been found to play a similar role in the progression of biliary intraepithelial neoplasias to CCs [16 , 17] . Unsurprisingly, both share a similar growth pattern, are poorly responsive to conventional chemotherapy and are seldom associated with a good prognosis [5 , 15] .…”

“…Synchronous pancreatobiliary cancers are rarely reported in literature and can pose significant diagnostic challenges to oncologists and the cancer multidisciplinary team. This is further complicated by the histological and anatomical similarities of biliary and pancreatic malignancies which hinders the identification and distinguishability of the clonal origin of these tumors [5] . Understanding the origin of synchronous tumors is essential as it has an impact on surgical and oncological treatment and follow-up strategies.…”

Vav1 Sustains the In Vitro Differentiation of Normal and Tumor Precursors to Insulin Producing Cells Induced by all-Trans Retinoic Acid (ATRA)

“…Based on recent evidence that in adult human pancreatic duct glands (PDGs), distinct niches of progenitor cells constitute a natural source of β cells for the purposes of regenerative medicine [42][43][44] and that PDGs might have a central role in the development of PDAC [45], human biliary tree stem/ progenitor cells and PDAC-derived cell lines were used to assess whether ATRA induces the differentiation of both cell systems towards a pancreatic islet fate by up-modulating the expression of Vav1.…”

Cellular Immunotherapy Targeting Cancer Stem Cells: Preclinical Evidence and Clinical Perspective

“…Numerous preclinical studies have indicated other surface markers potentially useful to identify or target CSCs: CD90, ALDH, CD47, CD44, CD24, microtubule-associated doublecortin-like kinase 1 (DCLK1) that are expressed in multiple cancer types with a higher expression in CSCs compared to other bulk tumor cells [ 82 , 97 , 106 , 107 ]. DCLK1 has been described as a CSC associated antigen in colon, pancreatic [ 108 , 109 , 110 ] and even in Cholangiocarcinoma (CCA) tumors [ 111 ]. Recently, preclinical findings supported promising results with adoptive immunotherapy based on DCLK1-CAR T lymphocytes against colorectal cancer (CRC) [ 107 ].…”