Dataset Information

Mucins in neoplasms of pancreas, ampulla of Vater and biliary system.

ABSTRACT: Tumors of the pancreas, the ampulla of Vater, and the extrahepatic and intrahepatic bile ducts have significant histological similarities due to the common embryonic origin of the pancreatobiliary system. This obviates the need for discovery of biomarkers with diagnostic and prognostic value for these tumors. Mucins, especially MUC-1, -2, -4 and -5AC, are important candidates for developing into such reliable biomarkers. Increased expression of MUC1 occurs in pancreatic ductal adenocarcinomas and is associated with increased degrees of dysplasia in pancreatic intraepithelial neoplasia (PanIN). Positive expression of MUC2 in intraductal papillary mucinus neoplasms (IPMN) of the intestinal type indicates high potential progression to invasive carcinoma with de novo expression of MUC1, while absence of MUC2 expression in IPMNs of gastric type implies low potential to malignant evolution. De novo MUC4 expression correlates to the severity of dysplasia in PanIN and is associated with a poor prognosis in patients with pancreatic ductal adenocarcinomas. In biliary intraepithelial neoplasia (BilIN), increased expression of MUC1 is associated with higher degrees of dysplasia. Intrahepatic cholangiocarcinomas (ICC) are characterized by increased expression of all glycoforms of MUC1. Positive MUC2 expression in intraductal papillary neoplasm of the bile ducts (IPNB) of the intestinal type indicates high malignant potential with de novo expression of MUC1 in the invasive element. Absent MUC2 expression in any degree of BilIN may prove useful in differentiating them from IPNB. De novo expression of MUC4 is associated with poor prognosis in patients with ICC or carcinoma of the extrahepatic bile ducts (EHBDC). High de novo expression of MUC5AC is found in all degrees of BilIN and all types of IPNB and ICC. The MUC5AC is useful in the detection of neoplastic lesions of the bile duct at an early stage. Increased expression of mucin MUC1 in carcinoma of the ampulla of Vater associated with unfavorable behavior of the tumor, such as lymph node metastasis, infiltration of the pancreas and duodenum, advanced TNM classification and worse prognosis. Patients with intra-ampullary papillary-tubular neoplasm (IAPN) of the pancreatobiliary immunophenotype did not show MUC2, while those of the intestinal immunophenotype are MUC2 positive. The expression of MUC4 is associated with poor prognosis in patients with carcinoma of the ampulla of Vater favoring metastasis and making them resistant to apoptosis. Moreover, it appears that MUC4 positivity correlates with recurrence of the tumor. Expression of MUC5AC is associated with the invasive potential of the tumor.

SUBMITTER: Moschovis D

PROVIDER: S-EPMC5064050 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Mucins in neoplasms of pancreas, ampulla of Vater and biliary system.

Moschovis Dimitrios D Bamias Giorgos G Delladetsima Ioanna I

World journal of gastrointestinal oncology 20161001 10

Tumors of the pancreas, the ampulla of Vater, and the extrahepatic and intrahepatic bile ducts have significant histological similarities due to the common embryonic origin of the pancreatobiliary system. This obviates the need for discovery of biomarkers with diagnostic and prognostic value for these tumors. Mucins, especially MUC-1, -2, -4 and -5AC, are important candidates for developing into such reliable biomarkers. Increased expression of MUC1 occurs in pancreatic ductal adenocarcinomas an ...[more]

PMID: 27795812

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Project description:LESSONS LEARNED:Panitumumab has no clinical activity in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC), possibly due to the foregut and midgut derivation of small bowel and ampulla.These results, along with findings from genomic characterization of SBA, suggest that SBA represents a unique intestinal malignancy and treatments should not be habitually extrapolated from colorectal cancer.Further studies evaluating the benefit of targeted therapies exclusively in SBA and AAC are warranted. BACKGROUND:Given the benefit of epidermal growth factor receptor (EGFR) monoclonal antibodies in colorectal cancer (CRC), we sought to evaluate the efficacy of panitumumab in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). METHODS:We conducted a single-center, open-label, single-arm, Bayesian phase II trial. The primary objective was response rate (RR). Panitumumab was administered at a dose of 6 mg/kg intravenously (IV) every 14 days. RESULTS:Nine patients (male/female 7:2, median age: 61 years [range: 40-74], Eastern Cooperative Oncology Group [ECOG] performance status 0/1: 2/7) were enrolled from September 2013 to October 2015. One patient had AAC (pancreaticobiliary subtype) and eight patients had SBA (three duodenal, five jejunal/ileal). Acneiform rash was the most common toxicity. The study was stopped early due to futility with no responses, stable disease (SD) in two patients, and progression of disease (PD) in seven patients. Median progression-free survival (PFS) and overall survival (OS) were 2.4 and 5.7 months, respectively. No patients had extended RAS mutations (exons 2/3/4), but two patients had BRAF G469A and one patient had PIK3CA H1074R mutations. CONCLUSION:Panitumumab had no clinically meaningful activity in patients with metastatic RAS wild-type SBA and AAC. Our findings may relate to the primarily midgut and foregut derivation of the small bowel and ampulla.

Project description:Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3-49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04-3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11-3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19-9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23-4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches.

Dataset Information

Mucins in neoplasms of pancreas, ampulla of Vater and biliary system.

Publications

Mucins in neoplasms of pancreas, ampulla of Vater and biliary system.

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