PMID- 9520947
OWN - NLM
STAT- MEDLINE
DCOM- 19980420
LR  - 20141120
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 78
IP  - 3
DP  - 1998 Mar
TI  - Amplification of c-erbB-2 in gastric cancer: detection in formalin-fixed, 
      paraffin-embedded tissue by fluorescence in situ hybridization.
PG  - 345-51
AB  - A total of 396 adenocarcinomas of the stomach were examined immunohistochemically 
      using antibodies specific for the internal domain of human c-erbB-2 protein. 
      Forty of these (consisting of 35 well-differentiated and 5 undifferentiated 
      types) overexpressed c-erbB-2, as evidenced by cytoplasmic membrane staining; 
      these tumors were further examined by fluorescence in situ hybridization using a 
      cosmid probe for 17q11.2-12 (c-erbB-2 locus) on formalin-fixed, paraffin-embedded 
      tissues. This technique enabled us not only to detect c-erbB-2 amplification on a 
      cell-by-cell basis, but also to compare the gene amplification with the protein 
      expression, observe topographical distribution, and establish quantitative 
      pictures of the amplification in vivo condition. In all 40 tumors, we observed 
      gene amplification and found that the cancer cell with the amplification 
      corresponded to the cells overexpressing c-erbB-2. In eight mucosal carcinomas, 
      signals were coalesced to one or two clusters, indicating that the amplified gene 
      resided in a homogeneous staining region (HSR). Among 32 carcinomas invading 
      beyond muscularis mucosae, approximately half were mostly composed of cells with 
      the amplification; the others had populations of tumor cells with and without 
      amplification, which were sometimes in separate zones or areas and sometimes 
      mixed together. In 22 cancers, the amplified genes were exclusively in HSR; 
      however, cancer cells with multiple scattered signals-suggesting that the 
      amplified genes were translocated to other chromosomes-were found exclusively in 
      6 tumors and concurrently with HSR in 4 tumors. These findings suggest that: (a) 
      the amplification produces c-erbB-2 in the HSR form generally early in the 
      carcinogenesis of gastric adenocarcinomas; and (b) in the process of cancer 
      development, the amplified gene is lost in some cancer cells by uneven 
      segregation of HSR in mitosis, whereas in others, it is kept in HSR or 
      translocated to other chromosomal positions, thereby preserving overexpression of 
      c-erbB-2 protein.
FAU - Ooi, A
AU  - Ooi A
AD  - Department of Pathology, Faculty of Medicine, Kanazawa University, Japan.
FAU - Kobayashi, M
AU  - Kobayashi M
FAU - Mai, M
AU  - Mai M
FAU - Nakanishi, I
AU  - Nakanishi I
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Fixatives)
RN  - 1HG84L3525 (Formaldehyde)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adenocarcinoma/*genetics/metabolism/pathology
MH  - Fixatives
MH  - Formaldehyde
MH  - Gene Amplification/*physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Paraffin Embedding
MH  - Receptor, ErbB-2/*genetics/metabolism
MH  - Stomach Neoplasms/*genetics/metabolism/pathology
EDAT- 1998/04/01 00:00
MHDA- 1998/04/01 00:01
CRDT- 1998/04/01 00:00
PHST- 1998/04/01 00:00 [pubmed]
PHST- 1998/04/01 00:01 [medline]
PHST- 1998/04/01 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1998 Mar;78(3):345-51.