Gastric Epithelial Dysplasia in the Natural History of Gastric Cancer: A Multicenter Prospective Follow-up Study zyxwvutsrqponmlkjihgfedcbaZYXWVU MASSIMO RUGGE,* FABIO FARINATI,’ RAFFAELE BAFFA,* FULVIA SONEGO,* FRANCESCO DI MARIO,’ GIOACCHINO LEANDRO,§ and FLAVIO VALIANTE? FOR THE INTERDISCIPLINARY GROUP ON GASTRIC EPITHELIAL DYSPLASIA Departments of *Pathology and +Gastroenterology, University of Padova. Padova; and ““S De Bellis” Gastroenterology Hospital, Castellana Grotte, Bari, Italy zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA See editorial on page 1543. Background/Aims: Because the precancerous signifi- cance of gastric epithelial dysplasia (GED) is still under debate, this study attempts to ascertain whether a pro- spective follow-up of GED can contribute to clarifying its clinical and pathological relationships with gastric cancer (GC). Methods: One hundred twelve patients with mild (Gl), moderate (G2), and severe (63) GED or diagnosed as indefinite for dysplasia were prospec- tively followed up with a standardized endoscopic and bioptic protocol. Results: Evaluation of GED outcome refers only to 93 patients with a follow-up period longer than 12 months. Regression of dysplasia was docu- mented in 36%, 27%, and 0% of Gl, 62, and 63 GED cases, respectively. Progression to more severe dyspla- sia or evolution into GC was detected in 21%, 33%, and 57% of Gl, 62, and 63 GED cases, respectively. Evolution into GC was documented for all grades of dysplasia and correlated significantly with high-grade atrophic gastritis. A high prevalence of early GC (86.9%) was also observed. Conclusions: GED is a pre- invasive lesion, and carcinomatous evolution increases proportionally with its histological grade. Bioptical fol- low-up is mandatory for all histological grades of GED and significantly increases the likelihood of GC being detected in its early stages. A lthough the incidence of gastric cancer (GC) is de- clining dramatically in western Europe and the United States, it still remains the second most common cancer in the world’ and is characterized by a very poor prognosis in its more advanced stages.2P3 Like other epithelial malignancies, GC is consistent with the theory of invasive cancer arising from a series of histological abnormalities that are the morphological counterparts of a number of genetic events in the multistep process of carcinogenesis. *-’ Gastric epithelial malignancies really consist of two pathological entities with different epidemiological, clinical, pathological, and biological characteristics.8 Intestinal-type GC predomi- nates in high-risk populations (epidemic type), is more frequent in the elderly, and is characterized by a histolog- ical pattern that mimics large bowel adenocarcinoma. The diffuse type is less common, occurring relatively more frequently in low-risk populations and mostly in younger people. Different precancerous lesions probably exist for intestinal and diffuse GC. At present, a putative sequential precancerous process has only been described in the morphogenesis of intestinal-type GC as an appar- ent continuum of lesions’ (i.e., superficial gastritis, atrophic gastritis, intestinal metaplasia [small intestinal and colonic type], dysplasia [adenomatous type or type 19310] and, finally, early and advanced GC). No well- defined precancerous lesions have yet been described for diffuse-type GC,4*6 which has been only tentatively linked with dysplasia arising in nonmetaplastic glands (type II).9*“912 Despite the introduction of new diagnostic methods, molecular biology, and a number of markers of preneoplastic and neoplastic lesions detectable in the serum or tissue,13-15 well-performed endoscopic sam- pling followed by conventional H&E staining still remains the first and most effective approach to the diagnosis of dysplasia.” Various histological classifications have been proposed for gastric epithelial dysplasia (GED),‘-“,” and high intraobserver and interobserver variations in its diagnosis have been emphasized.18-20 The considerable differences in the prevalence of GED reported by centers around the world probably reflect not only geographic variations’ but also, and more likely, significant differ- ences in the morphological criteria used for the diagnosis and grading of the lesion.” GED can often be found adjacent to superficial or advanced GC; in clinical prac- tice, it has been considered a warning marker of coexist- Abbreviations used in this paper: AGC, advanced gastric cancer: EGC, early gastric cancer; GC, gastric cancer; GC-nos, gastric cancer not otherwise specified; GED, gastric epithelial dysplasia. 6 1994 by the American Gastroenterologlcal Association 00185085/94/$3.00