title: Mucosal high apoptotic activity and low p21WAF1/CIP1 expression and submucosal low proliferative activity in superficially spreading early gastric cancers: comparison with the penetrating growth type.
abstract: In order to investigate cell kinetics and cell cycle regulator protein expression with reference to the growth pattern of early gastric carcinomas (EGCs), we evaluated a total of 240 EGCs with submucosal invasion clinicopathologically and 106 submucosal invasive lesions immunohistochemically. The incidence of lymph node metastasis was relatively high (36.4%) in the superficially spreading growth (SUP) type tumors whereas the penetrating growth (PEN) type had a low incidence (5.7%, P < 0.001) and correlated with submucosal tumor size. Ki67 labeling was lower in submucosal areas of the SUP-type tumors (median, 37.3%) than the PEN-type tumors (51.0%, P < 0.001). ssDNA labeling in the lamina propria, indicative of apoptotic activity, was higher in the SUP-type tumors (0.55%) than in PEN-type (0.30%, P < 0.01) lesions. The expression of cell cycle regulator p21WAF1/CIP1 was lower in the SUP-type tumors (lamina propria 15.6%, submucosa 2.6%) than in PEN-type tumors (lamina propria 26.5%, submucosa 4.4%, P < 0.05-0.001). In conclusion, differences in cell kinetics and p21WAF1/CIP1 expression might influence the growth pattern of EGCs. The SUP-type EGC, characterized by high apoptotic in the lamina propria and low proliferative activities in the submucosa, is associated with frequent lymph node metastasis, suggesting a strong correlation between tumor size in the submucosa and metastatic potential.
authors.affiliation: Department of Pathology, School of Medicine, Kitasato University, Kitasato, Sagamihara, Kanagawa, Japan. hanabi@med.kitasato-u.ac.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ichinoe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.forename: Shiro
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanabe
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Akino
authors.forename: Isao
authors.initials: I
authors.lastname: Okayasu
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002452:Cell Count; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D007700:Kinetics; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D004247:DNA