胃早发型和进展型管状腺癌的谱系分析：连续还是不连续？

Lineage analysis of early and advanced tubular adenocarcinomas of the stomach: continuous or discontinuous?

机构信息

Department of Pathology, Shiga University of Medical Science, Otsu, 520-2192 Japan.

出版信息

BMC Cancer. 2010 Jun 21;10:311. doi: 10.1186/1471-2407-10-311.

DOI:10.1186/1471-2407-10-311

PMID:20565940

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2898698/

Abstract

BACKGROUND

Eradication of early gastric carcinoma (GC) is thought to contribute to reduction in the mortality of GC, given that most of the early GCs progress to the advanced GCs. However, early GC is alternatively considered a dormant variant of GC, and it infrequently progresses to advanced GC. The aim of this study was to clarify the extent of overlap of genetic lineages between early and advanced tubular adenocarcinomas (TUBs) of the stomach.

METHODS

Immunohistochemical staining for p53 was performed using 28 surgically resected stomachs with 13 intramucosal and 15 invasive TUBs. By chromosome- and array-based comparative genomic hybridization (CGH), genomic copy number constitution was compared between the mucosal and invasive parts of the invasive TUBs and between the mucosal parts of the invasive and intramucosal TUBs, using 25 and 22 TUBs, respectively. TP53 mutation in exons 5-8 was examined in 20 TUBs.

RESULTS

Chromosomal CGH revealed that 4q+ and 11q+ were more common in advanced and early TUBs, respectively, whereas copy number changes in 8q and 17p showed no significant differences between early and advanced TUBs. However, array CGH revealed that, of the 13 intramucosal TUBs examined, loss of MYC (MYC-) and gain of TP53 (TP53+) was detected in 9 TUBs and MYC+ and/or TP53- was detected in 3 TUBs. Of the mucosal samples of 9 invasive TUBs, 7 showed MYC-/TP53+ and none showed MYC+ and/or TP53-. Of the 9 samples from the invasive parts, 1 (from submucosal cancers) showed MYC-/TP53+ and 6 (1 from submucosal and 5 from advanced cancers) showed MYC+ and/or TP53-. The latter 6 tumours commonly showed a mutant pattern (diffuse or null) in p53 immunohistochemistry, and 4 of the 6 tumours assessable for TP53 sequence analysis revealed mutations. The overall array CGH pattern indicated that, between the mucosal and invasive parts, genetic lineage was found discontinuous in 5 advanced cancers and continuous in 3 submucosal cancers.

CONCLUSIONS

Genetic lineages often differed between early and advanced TUBs. MYC-/TP53+ and MYC + and/or TP53- may be the signatures of dormant and aggressive TUBs, respectively, in the stomach.

摘要

背景

根除早期胃癌（GC）被认为有助于降低 GC 的死亡率，因为大多数早期 GC 会进展为晚期 GC。然而，早期 GC 也被认为是 GC 的休眠变体，很少会进展为晚期 GC。本研究旨在阐明胃早期管状腺癌（TUB）与晚期 TUB 之间遗传谱系的重叠程度。

方法

对 28 例手术切除的胃标本进行 p53 免疫组织化学染色，其中 13 例为黏膜内 TUB，15 例为侵袭性 TUB。通过染色体和基于阵列的比较基因组杂交（CGH），分别比较了 25 例和 22 例侵袭性 TUB 的黏膜和侵袭部分以及 13 例侵袭性 TUB 的黏膜部分的基因组拷贝数组成。对 20 例 TUB 进行了外显子 5-8 的 TP53 突变检测。

结果

染色体 CGH 显示，4q+和 11q+在晚期和早期 TUB 中更为常见，而 8q 和 17p 的拷贝数变化在早期和晚期 TUB 之间没有显著差异。然而，阵列 CGH 显示，在 13 例黏膜内 TUB 中，9 例 TUB 中检测到 MYC（MYC-）缺失和 TP53（TP53+）获得，3 例 TUB 中检测到 MYC+和/或 TP53-。在 9 例侵袭性 TUB 的黏膜样本中，7 例显示 MYC-/TP53+，无一例显示 MYC+和/或 TP53-。在 9 例侵袭性部分的样本中，1 例（来自黏膜下癌）显示 MYC-/TP53+，6 例（1 例来自黏膜下癌，5 例来自晚期癌）显示 MYC+和/或 TP53-。后 6 例肿瘤的 p53 免疫组织化学染色通常显示出突变模式（弥漫性或缺失性），其中 6 例可评估 TP53 序列分析的肿瘤中有 4 例显示突变。总体阵列 CGH 模式表明，在黏膜和侵袭部分之间，5 例晚期癌症的遗传谱系呈不连续，3 例黏膜下癌症的遗传谱系呈连续。