title: The expression of PTEN is associated with improved prognosis in patients with ampullary adenocarcinoma after pancreaticoduodenectomy.
abstract: BACKGROUND
  Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Somatic mutations of PTEN occur in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression is associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma, and pancreatic ductal adenocarcinoma.
  
  
  OBJECTIVE
  To study the expression of PTEN and its significance in ampullary adenocarcinoma (AA).
  
  
  METHODS
  We constructed tissue microarrays by using archival tissue from 92 patients (55 males, 37 females; median age, 63 years; age range, 37 to 87 years) with previously untreated AA who underwent pancreaticoduodenectomy at our institution. PTEN expression was evaluated by immunohistochemistry, scored semiquantitatively (based on staining intensity and percentage positive tumor cells), and correlated with clinicopathologic features and survival.
  
  
  RESULTS
  Of 92 cases, 23 (25.0%) were PTEN negative. Loss of PTEN expression correlated with lymph node metastasis (P = .004), advanced American Joint Committee on Cancer (AJCC) stage (P = .02), and higher frequency of recurrence (P = .03). Patients with PTEN-negative tumors had shorter disease-free survival (DFS, mean: 89.0 ± 20.8 months) and overall survival (OS, mean: 93.1 ± 19.1 months) than those with PTEN-positive tumors (DFS, mean: 161.4 ± 11.7 months, P = .01; OS, mean: 175.4 ± 11.0 months, P = .001). In multivariate analyses, PTEN expression was a prognostic factor for both DFS and OS, independent of AJCC stage, lymph node status, pathologic tumor (pT) stage, and differentiation.
  
  
  CONCLUSIONS
  Loss of PTEN expression is associated with poor DFS and OS in patients with AA after curative surgery. PTEN expression may be used as a prognostic marker for patients with resected AA.
authors.affiliation: From the Departments of Pathology (Drs S. Shroff, Rashid, and Huamin Wang), Gastrointestinal Medical Oncology (Drs Overman, R. T. Shroff, Hua Wang, Wolff, and Abbruzzese), and Surgical Oncology (Drs Chatterjee, Katz, Lee, and Fleming). The University of Texas M. D. Anderson Cancer Center, Houston.
authors.forename: Stuti
authors.initials: S
authors.lastname: Shroff
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.forename: Rachna T
authors.initials: RT
authors.lastname: Shroff
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Deyali
authors.initials: D
authors.lastname: Chatterjee
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Katz
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.forename: James L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: Jason B
authors.initials: JB
authors.lastname: Fleming
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater; D003138:Common Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human