Evidence that gastric pit dysplasia-like atypia is a neoplastic precursor lesion

Most gastric cancers develop via an intestinal metaplasia (IM)-dysplasia-carcinogenic pathway. We have noted that some patients with chronic gastritis have dysplasia-like atypia (DLA) limited to the pit epithelium but without involvement of the surface epithelium. We performed this study to determine the clinical and biological characteristics and outcome of DLA, to gain insight into its role in the pathogenesis of gastric cancer. The study consisted of 102 consecutive patients with resected gastric cancer, a separate cohort of patients (n = 166) with chronic gastritis and IM in their index gastric biopsies, and 44 controls. All specimens were evaluated for clinical and pathologic features of the cancer (in the resection cohort) and background mucosa. Of 102 patients with gastric cancer, 50 (49%) had DLA in areas of mucosa adjacent to or near either conventional dysplasia or cancer. This value was significantly higher than controls (DLA 6.8%; P < .0001). Gastric cancer patients with DLA showed a significantly higher age at presentation; intestinal-type adenocarcinoma; low-grade differentiation; stage 1 tumors; and a higher rate of chronic gastritis, IM, atrophy, and conventional dysplasia in the background mucosa compared to patients without DLA. DLA showed intestinal-type differentiation, and a higher Ki-67 rate and MUC6 positivity compared with IM. Of the 166 patients with biopsies, DLA was identified in 24 (14%). Upon follow-up, 38% of positive cases showed persistent DLA, whereas 25% progressed to conventional low-grade dysplasia. Based on these results, we conclude that DLA represents an important precursor lesion in gastric carcinogenesis and supports its interpretation as a neoplastic lesion.