Clinicopathological evaluation of biological behavior of submucosal invasive gastric carcinomas: relationship among lymph node metastasis, mucin phenotype and proliferative activity

Background: Gastric carcinomas have been classified into the differentiated and undifferentiated type, on the basis of its tendency to gland formation. As a result of recent advances in mucin histochemistry, mucin phenotypes of gastric carcinomas have been investigated. However, no consensus on the evaluation of the grade of malignancy of early gastric carcinomas regarding mucin phenotype expression has developed. To address this issue, we evaluated the lymph node metastasis rate and proliferative activity of a submucosal invasive (sm) gastric carcinoma according to mucin phenotype expression. Methods: In resected surgical specimens from 108 patients with a single sm gastric carcinoma, the association between clinicopathological factors and lymph node metastasis was evaluated. In all cases, immunohistochemical staining with human gastric mucin, Muc-2, and CD10 and mucin histochemical staining by paradoxical concanavalin A staining were performed. The mucin phenotypes were classified into gastric-type (G-type), intestinal-type (I-type), mixed gastric and intestinal type (M-type), or a lack of mucin (LOM), using these as markers. To evaluate the cell proliferative activity of the gastric carcinoma, proliferating cell nuclear antigen (PCNA) staining was also performed. Results: The rate of lymph node metastasis was higher for G-type sm carcinomas. A multivariate analysis showed that the G-type and lymphatic invasion were independent factors of lymph node metastasis. However, the PCNA-labeling index (PCNA-LI) was low for G-type carcinomas irrespective of the presence or absence of lymph node metastasis. In I-type carcinomas, PCNA-LI was significantly higher in cases that were positive for lymph node metastasis than in negative cases. Conclusion: G-type and lymphatic invasion are independent risk factors for lymph node metastasis of an sm gastric carcinoma, and proliferative activity may be a significant parameter for lymph node metastasis in cases with I-type carcinomas. J. Med. Invest. 54: 99-108, February, 2007