Mucin phenotype and molecular genetic analysis of gastric cancer

对胃癌的基因分析分为两部分进行综述。一、高分化早期胃腺癌粘蛋白表型及基因分析：将高分化早期胃腺癌分为胃型、肠型和胃肠混合型，并进行遗传分析。1)分化较好的粘液性肿瘤与细胞质粘蛋白的分化程度较低，并可能通过遗传进展使粘蛋白松散。2)单克隆性肿瘤细胞具有双相表型；3)部分病例癌灶与胃、肠表型并存。这是由于通过遗传进程和/或遗传分化而出现的亚克隆。4)肠上皮化生、正常粘膜及癌组织中均有hMLH1基因甲基化。总体而言，有许多高分化腺癌病例表现为胃型和混合型。这些表型多样性是由双向…赋予的肿瘤克隆的更多表型能力以及遗传进展和/或遗传分化。混合表型的腺癌细胞可能来自不完全化生的受损粘膜，也可能是具有混合表型能力的粘膜细胞。此外，我们还发现了从粘膜高分化癌发展到低分化癌的遗传途径。AFP-GC是一种罕见的侵袭性腺癌，具有复杂的组织学特征，包括髓样分化、肠母细胞分化和肝样分化。本研究对20例AFP-GC的多个病灶进行了显微解剖和杂合性丢失分析。大多数肿瘤是单克隆性的，有广泛的杂合性缺失(平均部分等位基因丢失0.79)。异质性LOH的存在提示AFP产生髓样癌、肠母细胞癌和肝细胞癌病灶可能是通过遗传进展和/或遗传分化来进化的。较少

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