PMID- 15095270
OWN - NLM
STAT- MEDLINE
DCOM- 20040520
LR  - 20151119
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 202
IP  - 4
DP  - 2004 Apr
TI  - Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) 
      immunoreactivity.
PG  - 430-8
AB  - Gastrointestinal stromal tumours (GISTs) are currently defined as mesenchymal 
      tumours of the gastrointestinal tract that express KIT receptor tyrosine kinase. 
      However, a small subgroup of tumours that fulfil the clinical and morphological 
      criteria for GISTs lack KIT expression. So far, the biological features of these 
      tumours have rarely been addressed. The present study describes seven 
      gastrointestinal stromal neoplasms that presented clinicopathological features 
      typical of GISTs but showed absence of CD117 expression as detected by 
      immunohistochemistry. The tumours originated from the stomach (n = 5), duodenum 
      (n = 1), and colon (n = 1), showing histologically either predominantly 
      epithelioid (n = 3), mixed spindled and epithelioid (n = 2), or 
      anaplastic/spindle cell (n = 2) type features. CD34 and alpha-smooth muscle actin 
      (alpha-SMA) positivity was present in four and three tumours, respectively. 
      Chromosomal analysis was performed in two cases, both showing losses of 
      chromosomes 14, 22, and 1p, which is the characteristic feature of GISTs. 
      Dual-colour interphase fluorescence in situ hybridization (FISH) analysis, 
      utilizing chromosome 1p-, 14-, and 22-specific probes, revealed a similar 
      cytogenetic profile in the remaining five tumour specimens. Mutational analysis 
      of exons 9, 11, 13, and 17 of KIT, and exons 12 and 18 of PDGFRA was performed in 
      all cases by denaturing high-pressure liquid chromatography (DHPLC) 
      pre-screening, followed by direct sequencing. None of the tumours showed KIT 
      mutant isoforms. Three tumours harboured PDGFRA exon 18 activating mutations; two 
      were Asp --> Val(842) missense substitutions and one was a DIM842-844 amino acid 
      deletion. KIT and PKC theta (protein activated in interstitial cells of Cajal and 
      GISTs) expression was determined by western immunoblotting of the total cell 
      lysates from three tumour biopsies. None of these three tumours expressed KIT, 
      while all specimens showed expression of PKC theta protein. These findings 
      indicate that there is a subgroup of KIT-negative GISTs that exhibit the same 
      morphological, cytogenetic, and molecular features as KIT-positive tumours. While 
      intragenic PDGFRA activating mutations are present in some of these tumours, the 
      oncogenic events underlying the pathogenesis of the others remain unknown.
CI  - Copyright 2004 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Debiec-Rychter, Maria
AU  - Debiec-Rychter M
AD  - Laboratory for Cytogenetics and Molecular Genetics of Human Malignancies, 
      Department of Human Genetics, Catholic University of Leuven, Belgium. 
      Maria.Debiec-Rychter@med.kuleuven.ac.be
FAU - Wasag, Bartosz
AU  - Wasag B
FAU - Stul, Michel
AU  - Stul M
FAU - De Wever, Ivo
AU  - De Wever I
FAU - Van Oosterom, Allan
AU  - Van Oosterom A
FAU - Hagemeijer, Anne
AU  - Hagemeijer A
FAU - Sciot, Raf
AU  - Sciot R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Neoplasm Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Blotting, Western
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/genetics
MH  - Female
MH  - Gastrointestinal Neoplasms/genetics/*metabolism/pathology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Male
MH  - Mesenchymoma/genetics/*metabolism/pathology
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Proto-Oncogene Proteins c-kit/genetics/*metabolism
MH  - Receptor, Platelet-Derived Growth Factor alpha/genetics
EDAT- 2004/04/20 05:00
MHDA- 2004/05/21 05:00
CRDT- 2004/04/20 05:00
PHST- 2004/04/20 05:00 [pubmed]
PHST- 2004/05/21 05:00 [medline]
PHST- 2004/04/20 05:00 [entrez]
AID - 10.1002/path.1546 [doi]
PST - ppublish
SO  - J Pathol. 2004 Apr;202(4):430-8. doi: 10.1002/path.1546.