BACKGROUND: Despite the widespread use of endoscopic mucosal resection (EMR) for intramucosal gastric carcinoma, there is no standardized therapy for those patients in whom the carcinoma is found, after EMR, to have invaded the submucosa.Our aim in this study was to examine the relationship between the clinicopathological features of submucosal invasive carcinomas and their incidence of nodal micrometastasis, as detected by anti-human cytokeratin immunohistochemistry, in order to assess the curative potential of submucosal carcinoma by EMR.METHODS: Fifty surgically resected submucosal gastric carcinomas which would have satisfied the absolute indications for EMR, except for the criterion of submucosal invasion, were examined. The extent of submucosal invasion was determined by measuring its vertical and horizontal spread. Immunohistochemical analysis was performed with anti-human cytokeratin antibody (CAM5.2).RESULTS: Three of 50 cases (6.0%) were positive for nodal metastasis by routine H&E examination. Nodal micrometastases were detected in 11 of 47 cases (23.4%). Statistical analysis revealed that both the depth and the width of carcinoma in the submucosa were significantly larger in cases with than in those without micrometastasis ( P = 0.019 and P = 0.006, respectively). The group with lymphatic invasion showed more frequent micrometastasis than the group without ( P = 0.014). There were no micrometastases in submucosal carcinomas whose submucosal invasion was less than 200 &mgr;m vertically and less than 320 &mgr;m horizontally.CONCLUSIONS: The present study indicates that differentiated gastric adenocarcinoma with minimal submucosal invasion (less than 200 &mgr;m vertically and less than 320 &mgr;m horizontally) and not accompanied by peptic ulcer or other risk factors, such as lymphatic invasion, can be considered as having high curative potential by EMR alone, without the necessity for further radical surgery.