Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up

Department of Pathology, University of Bonn, Bonn, Germany.
American Journal of Surgical Pathology (Impact Factor: 5.15). 07/2004; 28(7):875-82.
Source: PubMed


A broad histomorphologic spectrum of ampullary carcinomas of Vater make a reproducible histologic classification difficult. Using cytokeratin immunohistochemistry, we present a new classification of ampullary carcinomas and analyze their clinical significance. Fifty-five invasive carcinomas of Vater's ampulla were histologically classified into pancreaticobiliary, intestinal, and other types. Serial sections of all carcinoma specimens were additionally stained with antibodies to cytokeratins (CK7, CK20), apomucins (MUC1, MUC2, MUC5AC), CEA, CA19-9, Ki67, and p53. Follow-up of patients from 4 months to 22 years after surgery (mean interval, 51.6 months) was evaluated. Most carcinomas of the ampulla of Vater were of immunohistochemically pancreaticobiliary type (iPT, CK7+, CK20-; 54.5%) or intestinal type (immunohistochemically intestinal type [iIT], CK7-, CK20+; 23.6%). Some carcinomas of immunohistochemically "other" type (iOT both CK7+ and CK20+ or CK7- and CK20-; 21.8%) had precursor lesions of iIT or iPT. Carcinomas positive for MUC2 or CEA were associated with iIT (MUC2, P < 0.001; CEA, P = 0.003), whereas MUC5AC-positive carcinomas were related to iPT (P = 0.005). Our classification based on cytokeratin-immunohistochemistry correlated well with the histologic classification according to published criteria (kappa-coefficient = 0.398; P < 0.001). Furthermore, histologically unusual types could be histogenetically related to pancreaticobiliary duct mucosa or intestinal mucosa. Therefore, all 4 signet-ring cell carcinomas were iIT carcinomas. Thus, cytokeratin immunohistochemistry allows a reproducible, histogenetically based categorization of ampullary carcinomas. However, neither histopathologic nor immunohistochemical subgroups significantly correlated with clinical outcome in our German collective. The overall survival was significantly shorter in males (P = 0.032) and patients with positive nodal stage (N1 < N0; P = 0.0025).

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    • "These authors also reported that ampullary cancers of pancreatobiliary origin are more frequently accompanied by lymph node involvement and had a worse prognosis than carcinomas of an intestinal origin [39]. Zhou et al. reported in 2004 the use of cytokeratin and apomycin markers to assign ampullary cancers histologically and unambiguously to one of the two subgroups [13]. However, these methods are still not a popular standard today, even though Westgaard et al. showed that the histological subtype is an essentially more relevant prognostic factor than the otherwise typical affiliation to one of the anatomical subtypes of periampullary carcinomas [40]. "
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    ABSTRACT: Introduction. Although ampullary carcinoma has the best prognosis among all periampullary carcinomas, its long-term survival remains low. Prognostic factors are only available for a period of 10 years after pancreaticoduodenectomy. The aim of this retrospective study was to identify factors that influence the long-term patient survival over a 15-year observation period. Methods. From 1992 to 2007, 143 patients with ampullary carcinoma underwent pancreatic resection. 86 patients underwent pylorus-preserving pancreaticoduodenectomy (60%) and 57 patients underwent standard Kausch-Whipple pancreaticoduodenectomy (40%). Results. The overall 1-, 5-, 10-, and 15-year survival rates were 79%, 40%, 24%, and 10%, respectively. Within a mean observation period of 30 (0-205) months, 100 (69%) patients died. Survival analysis showed that positive lymph node involvement (P = 0.001), lymphatic vessel invasion (P = 0.0001), intraoperative administration of packed red blood cells (P = 0.03), an elevated CA 19-9 (P = 0.03), jaundice (P = 0.04), and an impaired patient condition (P = 0.01) are strong negative predictors for a reduced patient survival. Conclusions. Patients with ampullary carcinoma have distinctly better long-term survival than patients with pancreatic adenocarcinoma. Long-term survival depends strongly on lymphatic nodal and vessel involvement. Moreover, a preoperative elevated CA 19-9 proved to be a significant prognostic factor. Adjuvant therapy may be essential in patients with this risk constellation.
    HPB Surgery 03/2014; 2014(3):970234. DOI:10.1155/2014/970234
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    • "Patients with intestinal AVCs have a much better prognosis than those with pancreatobiliary AVCs.4 However, other studies have reported that histologic subgroup does not correlate with clinical outcomes.5-7 "
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    ABSTRACT: Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, β-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, β-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and β-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous β-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. Dysregulation of E-cadherin, β-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.
    Gut and Liver 01/2014; 8(1):94-101. DOI:10.5009/gnl.2014.8.1.94 · 1.81 Impact Factor
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    • "More recently studies have investigated additional markers such cytokeratin expression, mucin expression, microsatellite instability, and intestinal-specific markers to identify prognostically distinct subgroups of ampullary adenocarcinomas. [5], [7], [10]–[16] For example, expression of the intestinal markers, CDX-2 and CDX-1, were recently shown to correlate with improved OS in a cohort of 53 patients [13], but this finding was not validated in subsequent studies [5], [12]. Though these studies taken together have been suggestive of heterogeneity within ampullary adenocarcinomas, interpretation of these results has been limited by small sample size and variability in classification methodology. "
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    ABSTRACT: Adenocarcinomas of the ampulla of Vater are classified as biliary cancers, though the exact epithelium of origin for these cancers is not known. We sought to molecularly classify ampullary adenocarcinomas in comparison to known adenocarcinomas of the pancreas, bile duct, and duodenum by gene expression analysis. We analyzed 32 fresh-frozen resected, untreated periampullary adenocarcinomas (8 pancreatic, 2 extrahepatic biliary, 8 duodenal, and 14 ampullary) using the Affymetrix U133 Plus 2.0 genome array. Unsupervised and supervised hierarchical clustering identified two subtypes of ampullary carcinomas that were molecularly and histologically characterized. Hierarchical clustering of periampullary carcinomas segregated ampullary carcinomas into two subgroups, which were distinctly different from pancreatic carcinomas. Non-pancreatic periampullary adenocarcinomas were segregated into two subgroups with differing prognoses: 5 year RFS (77% vs. 0%, p = 0.007) and 5 year OS (100% vs. 35%, p = 0.005). Unsupervised clustering analysis of the 14 ampullary samples also identified two subgroups: a good prognosis intestinal-like subgroup and a poor prognosis biliary-like subgroup with 5 year OS of 70% vs. 28%, P = 0.09. Expression of CK7+/CK20- but not CDX-2 correlated with these two subgroups. Activation of the AKT and MAPK pathways were both increased in the poor prognostic biliary-like subgroup. In an independent 80 patient ampullary validation dataset only histological subtype (intestinal vs. pancreaticobiliary) was significantly associated with OS in both univariate (p = 0.006) and multivariate analysis (P = 0.04). Gene expression analysis discriminated pancreatic adenocarcinomas from other periampullary carcinomas and identified two prognostically relevant subgroups of ampullary adenocarcinomas. Histological subtype was an independent prognostic factor in ampullary adenocarcinomas.
    PLoS ONE 07/2013; 8(6):e65144. DOI:10.1371/journal.pone.0065144 · 3.23 Impact Factor
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