Mucin phenotype and molecular genetic analysis of gastric cancer

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Genetic analysis of gastric cancer is summarized in two parts. I. Mucin phenotype and genetic analysis of well differentiated early gastric adenocarcinoma : Well differentiated early gastric adenocarcinoma cases were classified into gastric, intestinal, and mixed gastric/intestinal phenotype, and were subjected to genetic analysis. 1) Well differentiated mucosal tumor with cytoplasmic mucin may become less differentiated and may loose mucin by genetic progression. 2) There are monoclonal tumor cells possessing biphasic phenotype, 3) Some cases show carcinoma foci with gastric and intestinal phenotype side by side. This is caused by subclonal emergence through genetic progression and/or genetic divergence. 4) Methylation of hMLHl was detected in intestinal metaplasia and even normal appearing mucosa as well as carcinoma portions. Altogether, there are many well differentiated adenocarcinoma cases showing gastric and mixed phenotype. These phenotypic diversity is conferred by bidirection … More al phenotypic ability of the tumor clones as well as genetic progression and/or genetic divergence. Adenocarcinoma cells with mixed phenotype may emerge from damaged mucosa with incomplete metaplasia or mucosal cells with mixed phenotypic ability. Furthermore, we identified genetic pathways from mucosal well differentiated carcinoma progressing to less differentiated forms. II. Genetic analysis of Alpha fetoprotein producing gastric cancer (AFP-GC) : AFP-GC is an unusual form of aggressive adenocarcinoma showing complex histological pictures including medullary pattern, enteroblastic, and hepatoid differentiation. In the present study, multiple foci from 20 cases of AFP-GC were microdissected and LOH analysis was performed. Most tumors were single clonal with extensive LOH (an average fractional allelic loss of0.79). Presence of heterogeneous patterns of LOH suggested that the AFP producing medullary, enteroblastic and hepatoid carcinoma foci may evolve through genetic progression and/or genetic divergence. Less