Fujii H, Ichikawa K, Takagaki T, Nakanishi Y, Ikegami M, Hirose S, Shimoda T
Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ko, Tokyo, 113-8421, Japan.
J Clin Pathol. 2003 Dec;56(12):942-9. doi: 10.1136/jcp.56.12.942.
Alpha fetoprotein (AFP) producing gastric cancer is an unusual form of aggressive adenocarcinoma with a complex histological picture, including enteroblastic and hepatoid differentiation.
To investigate the genetic events underlying the phenotypic diversity in AFP producing gastric cancer and the ability of these tumours to produce AFP ectopically.
Multiple foci from 19 AFP producing gastric adenocarcinomas were microdissected and loss of heterozygosity (LOH) analysis was performed with a panel of microsatellite markers on nine chromosomal arms.
For informative cases, LOH was most frequently detected on 17p (100%), followed by 13q (88%), 3p (87%), 5q and 9p (80%), 11q (70%), 18q (58%), 16q (53%), and 8p (50%). The average fractional allelic loss was 0.72. LOH was detected either homogeneously throughout the microdissected foci, or only in some parts of the neoplastic foci for each case. Heterogeneous patterns of LOH indicated genetic progression and/or divergence in clonal evolution. Furthermore, in six cases with heterogeneous LOH of 13q, 13q LOH was restricted to immunohistochemically AFP positive neoplastic foci.
AFP-GC arises as an aggressive clone with extensive LOH and high fractional allelic loss. The presence of heterogeneous patterns of LOH suggested that the AFP producing carcinoma foci might evolve through genetic progression and/or genetic divergence. Silencing of the crucial gene on 13q may be involved in the acquisition of the AFP producing phenotype.
产生甲胎蛋白（AFP）的胃癌是侵袭性腺癌的一种特殊形式，具有复杂的组织学表现，包括成肝细胞样和肝样分化。
研究产生AFP的胃癌表型多样性背后的遗传事件，以及这些肿瘤异位产生AFP的能力。
对19例产生AFP的胃腺癌的多个病灶进行显微切割，并用一组微卫星标记对9个染色体臂进行杂合性缺失（LOH）分析。
对于有信息价值的病例，LOH最常出现在17p（100%），其次是13q（88%）、3p（87%）、5q和9p（80%）、11q（70%）、18q（58%）、16q（53%）和8p（50%）。平均等位基因缺失率为0.72。在每个病例中，LOH要么在整个显微切割病灶中均匀检测到，要么仅在肿瘤病灶的某些部分检测到。LOH的异质性模式表明克隆进化中的基因进展和/或分歧。此外，在6例13q存在异质性LOH的病例中，13q LOH仅限于免疫组化AFP阳性的肿瘤病灶。
AFP产生的胃癌（AFP-GC）是作为具有广泛LOH和高等位基因缺失率的侵袭性克隆出现的。LOH的异质性模式表明，产生AFP的癌灶可能通过基因进展和/或基因分歧而演变。13q上关键基因的沉默可能与AFP产生表型的获得有关。
