Evidence That Dysplasia Begins in the Bases of the Pits in the Pathogenesis of Gastric Cancer
AT Agoston, GY Lauwers, RD Odze. Brigham & Womens Hospital, Boston, MA; Massachusetts General Hospital, Boston, MA
Background: Intestinal-type gastric cancer is believed to develop via an intestinal metaplasia-dysplasia-carcinoma pathway. Anecdotally, we have noted that dysplasia-like atypia may be limited to the deep pit epithelium, without surface epithelium involvement, particularly in the stomach of patients with gastric cancer. We hypothesized that this type of epithelial alteration may represent an early form of dysplasia [Pit Dysplasia (PD)]. The aim of this study was to evaluate the clinical, pathologic, and biologic features of PD in an attempt to determine if it is a significant precursor to gastric cancer.
Design: Routinely processed tissue sections from 102 randomly selected resection specimens from patients with gastric cancer (mean age 67; M/F ratio 1.6), and from 22 patients with chronic gastritis (mean age 56.8; M/F ratio 1.8) but without cancer (controls), were evaluated for a wide variety of gross and microscopic features. A subset of 30 study cases were also immunostained for Ki67, E-Cadherin, and p53, and evaluated for the presence and degree of positivity in areas of intestinal metaplasia (IM), PD, and carcinoma.
Results: PD was present in 50/102 (49%) study patients compared to only 9% of controls (p<0.05). Patients with PD showed an older mean age at diagnosis (71 vs. 64 years, p=0.02), but a similar M/F ratio compared to patients without PD. Pathologically, gastric cancers with PD showed a significantly increased proportion of intestinal-type adenocarcinomas (82% vs. 37%, p<0.01), a higher degree of tumor differentiation (p<0.01), lower overall pathologic stage (p=0.04), an increased association with chronic gastritis (p<0.01) and a significantly higher proportion of cases with IM (40% vs. 13%, p<0.01) and conventional (full pit) dysplasia (44% vs. 4%, p<0.01) compared to study cases without PD. PD was situated adjacent to neoplasia in 72% of cases (low-grade: 24%, high-grade dysplasia: 26%, carcinoma: 66%) and distant from the neoplasia in 28%. The degree of Ki67 and p53 staining increased progressively, and significantly, in areas of IM, PD, and cancer, whereas E-Cadherin staining decreased.
Conclusions: Dysplasia-like changes limited to the deep portions of the pits, without surface epithelium involvement, probably represents an important histologically identifiable precursor to gastric cancer. Further prospective biopsy studies are needed to determine the risk of neoplastic progression in patients with PD detected in mucosal biopsy specimens.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 58, Tuesday Afternoon