Expression of p53, AMACR, β-Catenin, and TFF-1 in Pyloric Gland Adenoma of the Stomach and the Duodenum
MC Wang, JR Scudiere, EA Montgomery, ZE Chen. Northwestern University Feinberg School of Medicine, Chicago, IL; Johns Hopkins Medical Institution, Baltimore, MD; Caris Cohen Diagnostics, Newton, MA
Background: Pyloric gland adenomas (PGAs) are recently described rare neoplasms that are clinically and histopathologically distinct from conventional gastric foveolar type adenomas (GFTAs). Despite their bland histologic appearance, PGAs are frequently associated with dysplasia and invasive carcinoma. To date, the molecular tumorigenesis of PGAs has not been elucidated.
Design: We studied 14 PGAs (9 from stomach and 5 from duodenum) from 7 patients (mean age of 68), 4 of which had associated invasive carcinoma. For comparison, we also studied 7 GFTAs (all from stomach) from 6 patients (mean age of 48.5). Unstained sections of tumors were obtained from Johns Hopkins Medical Institutions and immunohistochemical stains were performed to detect the expression of p53, AMACR, β-catenin, and TFF-1 in PGAs as compared to GFTAs. Stained sections were reviewed by 2 pathologists. For p53 and AMACR, greater than or equal to 5% staining in the neoplastic cells was considered positive. For β-catenin and TFF-1, abnormal staining patterns were determined by comparison with adjacent normal mucosa. Results were statistically analyzed via Fisher's exact test.
Results: Ten (71.4%) PGAs stained positive for p53, compared to 1 (16.7%) for GFTAs (p=0.02). Additionally, PGAs with associated invasive carcinoma tended to stain p53 more intensely (>50% of neoplastic cells are positive). For β-catenin, all 14 (100%) PGAs were positive for cytoplasmic staining, while only 4 (66.7%) GFTAs were positive (p=0.03). Eight (57.1%) PGAs showed positive nuclear staining, as compared to 2 (33.3 %) GFTAs (p=0.36). In normal gastric mucosa, TFF-1 stains in a linear, apical pattern. However, PGAs demonstrate a diffuse, granular, cytoplasmic staining pattern, which was also seen in associated invasive carcinomas. Seven (50%) PGAs also showed overexpression of AMACR.
Conclusions: The majority of PGAs show p53 upregulation that is significantly greater compared to GFTAs. This finding supports that PGAs are a distinct entity, behaving more aggressively than GFTA, given that p53 overexpression is often seen as a late event in malignant transformation. The abnormal staining patterns of β-catenin in PGAs may imply involvement of the Wnt/β-catenin pathway in their tumorigenesis. AMACR overexpression and abnormal TFF-1 staining patterns in PGAs are in keeping with their pre-cancerous nature and warrant further study.
Monday, March 22, 2010 1:00 PM
Poster Session II # 77, Monday Afternoon