title: Aberrant expression of p53, p21, cyclin D1, and Bcl2 and their clinicopathological correlation in ampullary adenocarcinoma.
abstract: Previous studies on the molecular alterations in ampullary adenocarcinoma (AA) are limited, and little is known about their clinical implications. The objective of this study is to examine the expression of p53, p21, cyclin D1, and Bcl2 and their clinical significance in patients with AA. Tissue microarrays were constructed using archival tissue from 92 patients with AA who underwent pancreaticoduodenectomy at our institution. Each tumor was sampled in triplicate with a 1.0-mm punch from representative areas. The expression of p53, p21, cyclin D1, and Bcl2 was evaluated by immunohistochemistry, and the staining results were correlated with clinicopathological features and survival. Among 92 cases studied, overexpression of p53, p21, cyclin D1, and Bcl2 was observed in 58.7%, 39.2%, 71.7%, and 5.4% of tumors, respectively. Patients whose tumor showed high level of cyclin D1 expression had higher risk of disease recurrence (P = .02) and worse recurrence-free and overall survivals after pancreaticoduodenectomy than did those with no or low cyclin D1 expression (P = .027 and P = .02, respectively). In multivariate analysis, cyclin D1 expression was an independent prognostic factor for both recurrence-free and overall survival (P < .05). However, there was no significant correlation between p53, p21, or Bcl2 expression and survival (P > .05). Our study showed that p53, p21, and cyclin D1, but not Bcl2, are frequently overexpressed in AAs. Cyclin D1 overexpression is associated with increased risk of disease recurrence and worse survival in patients with AA after resection.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Rongjun
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Michael
authors.initials: M
authors.lastname: Overman
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Deyali
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Stuti
authors.initials: S
authors.lastname: Shroff
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Katz
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Fleming
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. Electronic address: hmwang@mdanderson.org.
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D003138:Common Bile Duct Neoplasms / Q000401:mortality / Q000503:physiopathology* / Q000601:surgery; D019938:Cyclin D1 / Q000096:biosynthesis*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016577:Pancreaticoduodenectomy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1
keywords: Ampullary adenocarcinoma; Bcl2; Cyclin D1; Survival; p21; p53