Diagnostic Value of HMGAs, P53 and β-Catenin in Discriminating Adenocarcinoma from Adenoma or Reactive Atypia in Ampulla and Common Bile Duct Biopsies
Vladislav Zakharov, Bing Ren, Qi Yang, McMahon Loralee, Wenqing Cao. University of Rochester Medical Center, Rochester, NY
Background: Interpretation of biopsies from the ampulla of Vater and common bile duct are often challenging due to small sample sizes, frequent acute and chronic inflammation, and reactive changes. The markers explored in the previous studies are not widely used clinically due to low sensitivity, specificity or technique difficulty. We investigated the expression patterns of HMGA1, HMGA2, β-catenin and p53 in the biopsy specimens to evaluate the potential diagnostic value of these proteins in differentiating adenocarcinoma from reactive atypia or adenoma.
Design: 48 biopsies (10 from common bile duct and 38 from ampulla) were selected for immunohistochemical studies, which included 14 reactive atypia, 12 adenoma and 22 adenocarcinoma cases. Patterns of expression of HMGAs, p53 and β-catenin were evaluated and the associations of their expression with clinicopathological factors were analyzed.
Results: Expression of HMGA1 was seen in 22% of reactive atypia, 42% adenoma, and 91% adenocarcinoma. HMGA2 was positive in 17% of reactive atypia, 42% adenoma, and 86% of adenocarcinoma. Staining intensity of HMGA1 or HMGA2 was also significantly higher in adenocarcinoma compared to adenoma or reactive atypia. Interestingly, expression of both HMGA1 and HMGA2 was found in 86% of adenocarcinoma, 0% of reactive atypia and 8% of adenoma cases (p<0.001). 8 of 48 cases had initial nonmalignant diagnosis were diagnosed with carcinoma by either follow-up biopsy/resection specimens or imaging proven metastasis. 75% of them were stained positive with both HMGA1 and HMGA2. 100% of them were either HMGA1 or HMGA2 positive. P53 and β-catenin did not demonstrate significant differences among reactive atypia, adenoma and carcinoma.