PMID- 16785766
OWN - NLM
STAT- MEDLINE
DCOM- 20060804
LR  - 20061115
IS  - 1015-2008 (Print)
IS  - 1015-2008 (Linking)
VI  - 73
IP  - 1
DP  - 2006
TI  - How wild-type TP53 is inactivated in undifferentiated-type gastric carcinomas: 
      analyses of intratumoral heterogeneity in deletion and mutation of TP53.
PG  - 40-9
AB  - OBJECTIVE: In undifferentiated-type gastric carcinoma (UGC), inactivation of TP53 
      is infrequent at early stages and comparable to tubular adenocarcinomas (TUBs) at 
      advanced stages. To clarify how TP53 inactivation relates to histogenesis of 
      UGCs, we examined p53 alterations in multiple samples of individual UGCs. 
      METHODS: We used 27 UGCs including 12 mixed types with minor tubular component 
      (TC) and 16 with a layered structure (LS), a histological remnant of incipient 
      signet ring cell carcinoma (SIG). We examined p53 expression 
      immunohistochemically and analyzed loss of heterozygosity (LOH) with four 
      microsatellite markers within 17p13.1 in multiple microdissected samples. DNA 
      sequence of mutation hot spots in TP53 was determined in representative samples 
      of each tumor. RESULTS: In the mixed-type UGCs, 5 and 1 of the 8 tumors without 
      LS showed global and regional loss of wild-type TP53, respectively, through 
      mutation and LOH, and one fourth of the tumors with LS showed the regional loss. 
      In the tumors with the mutation, the mutation pattern was identical between TC 
      and poorly differentiated major component. CONCLUSION: The inactivation of 
      wild-type TP53 is an earlier event before dedifferentiation of TUB to mixed-type 
      UGC, but is less frequent and a later event in a subset of mixed-type UGC 
      deriving from SIG. .
FAU - Yoshimura, Akinobu
AU  - Yoshimura A
AD  - Department of Pathology, Shiga University of Medical Science, Otsu, Japan.
FAU - Sugihara, Hiroyuki
AU  - Sugihara H
FAU - Ling, Zhi-Qiang
AU  - Ling ZQ
FAU - Peng, Dun-Fa
AU  - Peng DF
FAU - Mukaisho, Ken-ichi
AU  - Mukaisho K
FAU - Fujiyama, Yoshihide
AU  - Fujiyama Y
FAU - Hattori, Takanori
AU  - Hattori T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Pathobiology
JT  - Pathobiology : journal of immunopathology, molecular and cellular biology
JID - 9007504
SB  - IM
MH  - Adenocarcinoma/*genetics/*pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Base Sequence
MH  - DNA Mutational Analysis
MH  - Female
MH  - *Genes, p53
MH  - Humans
MH  - Immunohistochemistry
MH  - Loss of Heterozygosity
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Mutation
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Stomach Neoplasms/*genetics/*pathology
EDAT- 2006/06/21 09:00
MHDA- 2006/08/05 09:00
CRDT- 2006/06/21 09:00
PHST- 2005/12/28 00:00 [received]
PHST- 2006/03/01 00:00 [accepted]
PHST- 2006/06/21 09:00 [pubmed]
PHST- 2006/08/05 09:00 [medline]
PHST- 2006/06/21 09:00 [entrez]
AID - 93090 [pii]
AID - 10.1159/000093090 [doi]
PST - ppublish
SO  - Pathobiology. 2006;73(1):40-9. doi: 10.1159/000093090.