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Background: Our previous studies have demonstrated the significant role of the generative cells of intestinal metaplasia (IM) expressing brain (fetal)-type glycogen phosphorylase (BGP) (BGP-IM) as a premalignant lesion of intestinal-type adenocarcinoma. The aims of the present study were to investigate the incidence of BGP-IM in gastric biopsy specimens and to establish BGP-IM as a predictor of the coexistence of accessory carcinoma and/or metachronous cancers before and after local treatment for early gastric carcinoma., Methods: We studied the incidence of BGP-IM in eight endoscopic biopsy specimens of methylene blue-positive mucosa of the stomach obtained from patients with multiple gastric carcinomas (n = 14), a single carcinoma (n = 25), and atrophic gastritis (n = 20)., Results: BGP positivity was 93.3% in the multiple carcinomas and 80.0% in the single carcinomas. The incidences of BGP-IM (mean percentage +/- SD) in the stomachs with multiple carcinomas, single carcinoma, and atrophic gastritis were 83.2% +/- 22.8%, 36.5% +/- 41.3%, and 7.1% +/- 18.0%, respectively. The incidence was significantly higher in the stomachs with multiple carcinomas than in those with a single carcinoma or those with atrophic gastritis (P < 0.001)., Conclusion: It is suggested that the frequent appearance of BGP-IM reflects the high potential of carcinogenesis of intestinal-type gastric cancer, and that the involvement of BGP-IM in more than 50% of the eight biopsies may be a predictor of the coexistence of accessory and/or metachronous carcinoma before and after local treatment for early gastric carcinoma.

Purpose: Although reports have suggested that differentiated gastric carcinomas have different phenotypes, i.e., gastric and intestinal type, this classification is complicated and can be confusing. Our previous studies have demonstrated a close relationship between carcinogenesis in differentiated-type gastric cancer and the expression of brain (fetal)-type glycogen phosphorylase (BGP). The purpose of this study was to investigate the relationship between the mucin phenotype of gastric carcinoma and BGP expression., Methods: Ninety-six specimens of gastric carcinoma were studied using specific anti-BGP antibody. Correlation of BGP expression with intestinal and gastric phenotypes was determined with the anti-mucin antibodies, HGM, CD10, and MUC2., Results: BGP was expressed in 82.6% (38/46) of differentiated type and in 24.0% (12/50) of undifferentiated type carcinomas. The incidence of BGP positivity was significantly greater in the differentiated-type carcinoma than in the undifferentiated type (P < 0.001). The proportions of gastric, mixed and intestinal types in differentiated and undifferentiated gastric carcinomas were 13.0%, 47.8%, and 39.2%, and 56.0%, 32.0%, and 12.0%, respectively. In both differentiated and undifferentiated types, the phenotype of gastric and intestinal mucin expression corresponded very well with BGP expression, that is, more than 90% of carcinomas with gastric type did not express BGP, whereas approximately 90% of carcinomas with intestinal type did express BGP., Conclusions: The classification of gastric and intestinal phenotypes of gastric carcinoma in terms of BGP expression was simpler and clearer than such classification in terms of mucin immunohistochemistry. It is suggested that BGP is a useful biomarker for the classification of intestinal and gastric type carcinoma of the human stomach, including classification from the carcinogenetic point of view.

'de novo' carcinogenesis has been advocated besides 'adenoma carcinoma sequence' as another dominant pathway leading to colorectal carcinoma. Our recent study has demonstrated that the distribution of brain (fetal)-type glycogen phosphorylase (BGP) positive foci (BGP foci) has a close relationship with the location of 'de novo' carcinoma. The aims of the present study are to investigate genetic alteration in the BGP foci and to characterize them in the 'de novo' carcinogenesis. 17 colorectal carcinomas without any adenoma component expressing both immunoreactive p53 and BGP protein were selected from 96 resected specimens from our previous study. Further investigations to examine the proliferating cell nuclear antigen (PCNA)-labelling index, and the p53 and the codon 12 of K-ras mutation using the polymerase chain reaction-single strand conformation polymorphism were performed in the BGP foci, BGP negative mucosa and carcinoma. The BGP foci were observed sporadically in the transitional mucosa adjacent to the carcinoma in all cases. The PCNA labelling index in the BGP foci was significantly higher than that in the BGP negative mucosa (P< 0.001). p53 mutations were observed in 8 carcinomas, but no K-ras mutation was detected. Interestingly, although none of the overexpressions of p53 protein was detected immunohistochemically in the BGP positive foci, the p53 gene frequently (41.2% of the BGP foci tested) mutated in spite of no K-ras mutation. The present study demonstrates potentially premalignant foci in the colorectal transitional mucosa with frequent p53 gene mutation. It is suggested that BGP foci are promising candidates for the further investigation of 'de novo' colorectal carcinogenesis., (Copyright 2001 Cancer Research Campaign.)

Background: Multivariate analyses has shown that the status of lymph node metastasis and the depth of tumor penetration through the gastric wall are the most important prognostic factors in patients with advanced gastric carcinoma after curative operation. A clinicopathological study was carried out to clarify a simple and optimal prognostic indicator for early gastric cancer., Methods: Retrospective analyses of 982 patients with early gastric cancer (562 with mucosal [M] and 420 with submucosal [SM] tumor) treated by gastrectomy with D2 lymph node dissection were performed., Results: The incidence of lymph node metastasis from M and SM tumors was 2.5% (14/562) and 20.2% (85/420), respectively. There were no apparent prognostic indicators in patients with M tumors. In patients with SM tumors, the cancer-specific 5-year survival of those with lymph node metastasis was significantly lower than that of those without such metastasis (77.6% vs 98.2%; P < 0.001). An sharp decrease in survival was seen between patients with two positive nodes and those with three positive nodes, and the cancer-specific 5-year survival rate of patients with three or more metastatic lymph nodes was significantly lower than that of those with one or two nodes (P < 0.001; univariate analysis). Multivariate analysis revealed that the involvement of three or more lymph nodes was the sole independent prognostic determinant (P = 0.016); the level of nodal metastasis was not an independent prognostic factor (P = 0.384). All patients with N2 lymph node echelons (according to the Japanese Research Society for Gastric Cancer classification of the draining lymph nodes of the stomach) in the group with one or two positive nodes survived for more than 5 years., Conclusion: The sole independent prognostic factor in SM gastric cancer is the involvement of three or more metastatic lymph nodes. We suggest that this simple prognostic indicator for the follow-up of early gastric cancer, and this could lead to potentially effective adjuvant chemotherapy.