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

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.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.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.Gastric cancer remains the second most common cause of cancer-related deaths worldwide, despite a recent decrease in its mortality in developed countries [1]. Gastric carcinomas (GCs) are classified morphologically into 2 major categories: tubular-forming type and diffuse type [2,3] and, in staging, into early cancers (