Carcinoma of the Ampulla of Vater Associated With or Without Adenoma: A Clinicopathologic Analysis of 198 Cases With Reference to p53 and Ki-67 Immunohistochemical Expressions

Abstract

Adenomatous areas are found frequently within or in the vicinity of carcinoma of the ampulla of Vater. This makes definite diagnosis difficult in the preoperative examination. The adenoma-carcinoma development hypothesis is generally accepted for colorectal tumors. Recently, a genetic alteration model during colorectal tumor development has attracted much attention, leading to various studies. We studied clinicopathologic features, prognostic factors, and the alteration of the p53 tumor suppressor gene using p53 immunohistochemical staining in pure adenomas, pure carcinomas, and carcinomas with adenomatous areas. A proliferative activity of the tumors using Ki-67 was also evaluated. Nine cases of pure adenoma and 198 cases of carcinoma of the ampulla of Vater were selected for this study. Among the 198 cases of the carcinoma, 83 cases (42%) had adenomatous areas. Positivity of p53 immunohistochemical staining was 0% in pure adenomas, 36% in the adenomatous areas of carcinomas with adenomatous areas and 62% in the carcinomatous areas of carcinomas with adenomatous areas, and 56% in pure carcinoma. Accumulation of p53 protein and the Ki-67 labeling index revealed no significant difference in prognosis. The clinicopathological factors examined were as follows: degree of invasion of the surrounding tissue, such as duodenal wall; pancreatic parenchyma; the presence or absence of lymphatic permeation; venous invasion; perineural invasion; the presence of regional lymph node metastasis; and TNM stage. Each of the clinicopathological factors showed a significant difference. Multivariate analysis revealed strong predictors for a worse prognosis: presence of lymphatic permeation, invasion of the pancreas, and perineural invasion. In conclusion, our results are consistent with the adenoma-carcinoma development hypothesis. It would seem that the molecular events leading to p53 accumulation in neoplasms of the ampulla of Vater occur relatively late during the oncogenetic process. Moreover, we think it may be useful to refer to the p53 overexpression in the diagnosis of ampullary tumors.

Expression of CD24, P-cadherin and S100A4 in tumors of the ampulla of Vater

“…4,5,[29][30][31] In our series, 74% of patients with ampullary carcinomas had evidence of coexisting adenomas which is in line with the literature reporting synchronous lesions in 30-91% of cases. 4,5 Differentiating normal mucosa with reactive atypia from dysplasia or dysplasia from invasive carcinoma can be challenging or even impossible in bioptic material. Markers for ampullary dysplasia or invasive carcinoma could therefore be of great diagnostic value.…”

“…[1][2][3] In up to 91% of cases, residual adenomas can be detected in the tumor periphery, indicating an adenoma-carcinoma sequence similar to that observed in colorectal cancer. 4,5 Patients commonly present early with obstructive jaundice due to neoplastic occlusion of the ampullary orifice. 6 Early detection but also biologic differences are held responsible for the better prognosis of ampullary tumors following pancreaticoduodenectomy compared with other periampullary tumors (median survival 30-50 months, 5-year survival rate 21-64%).…”

Clinical practice guidelines for the management of biliary tract cancers 2015: the 2nd English edition

“…Adenoma lesion is often seen around carcinoma lesion [242][243][244] and the abnormal findings of oncogene and tumor suppressor gene in adenoma are also reported [244,245].…”

Lack of Detectable Alterations in Immune Responses during Sublingual Immunotherapy in Children with Seasonal Allergic Rhinoconjunctivitis to Grass Pollen

“…Several in vitro and in vivo studies have shown that SIT induces a shift from a TH2-cell cytokine secretion profile, interleukin (IL)-4, IL-5 and IL-13, with secondary IgE production to a TH1-cell type, interferon (IFN)-γ [12,13,14,15], although there is conflicting evidence on the mechanisms involved.…”