PMID- 15753987
OWN - NLM
STAT- MEDLINE
DCOM- 20050728
LR  - 20151119
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 26
IP  - 4
DP  - 2005 Apr
TI  - Clinicopathological relevance of HER2/neu and a related gene-protein cubic 
      regression correlation in colorectal adenocarcinomas in Taiwan.
PG  - 933-43
AB  - While HER2/neu receptor tyrosine kinase is involved in various malignancies, 
      studies on colorectal adenocarcinoma (CRC) remain controversial. To try to 
      clarify the role played by HER2/neu in CRC, sixty-seven CRC patients in Taiwan 
      were analyzed. For this analysis, we used normalized dual-color fluorescence in 
      situ hybridization (FISH) and Photoshop-aided immunohistochemistry (IHC) between 
      cancers and their autologous non-neoplastic epithelia. The results revealed that 
      HER2/neu status was unrelated to age, sex, location and positive-nodal 
      percentage. Intramucosal carcinomas had earlier HER2/neu protein upregulation 
      than regional stromal invasion within Dukes' A, and had a gene level that had not 
      risen yet. Both gene gains and protein increases were significant in later stages 
      in regards to volumetric progression and nodal-metastatic Dukes' stage. Overall, 
      there were 1.53-fold (gene) and 1.81-fold (protein) increases from non-neoplastic 
      enterocytes to CRCs. The upregulating directions of gene (88%) and protein (88%) 
      presented symmetric agreement. Most CRCs exhibited low to intermediate levels of 
      HER2/neu overexpression with double-minute gene amplicons and cytosolic HER2/neu 
      proteins. Normalized FISH and IHC showed high cubic-regression correlation, 
      especially in Dukes' C. According to the correlation curve, the points with IHC 
      index >2.41 and FISH ratio >1.22 defined the area where 
      gene-amplification-dependent HER2/neu overexpression was present. Eleven (16%) 
      patients had values above the cut-off point (IHC = 2.41 and FISH = 1.22), 
      including 7 (10%) cases in cytosolic and 4 (6%) cases in membranous HER2/neu 
      overexpressions. The results suggest that HER2/neu plays a crucial role in CRC 
      tumorigenicity with gene-amplification-independent transcriptional activations 
      early in the carcinogenesis, and gene-amplification-dependent overexpression 
      later in the advanced stages. This indicates that HER2/neu can be a good 
      biological marker for selecting patients that may improve under therapies that 
      employ adequate HER2/neu-targeting strategies.
FAU - Li, Jhy-Wei
AU  - Li JW
AD  - Graduate Institute of Medical Sciences, National Defense Medical Center, National 
      Defense University, Neihu PO Box 90048-501, Taipei, Taiwan 114, ROC.
FAU - Chuang, Tzu-Chao
AU  - Chuang TC
FAU - Yang, An-Hang
AU  - Yang AH
FAU - Hsu, Chien-Kang
AU  - Hsu CK
FAU - Kao, Ming-Ching
AU  - Kao MC
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adenocarcinoma/*genetics/*pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*analysis
MH  - Cell Transformation, Neoplastic
MH  - Colorectal Neoplasms/*genetics/*pathology
MH  - Female
MH  - *Gene Expression Profiling
MH  - *Genes, erbB-2
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - *Neoplasm Staging
MH  - Prognosis
MH  - Receptor, ErbB-2/analysis/*biosynthesis/*genetics
MH  - Regression Analysis
MH  - Taiwan
MH  - Up-Regulation
EDAT- 2005/03/09 09:00
MHDA- 2005/07/29 09:00
CRDT- 2005/03/09 09:00
PHST- 2005/03/09 09:00 [pubmed]
PHST- 2005/07/29 09:00 [medline]
PHST- 2005/03/09 09:00 [entrez]
PST - ppublish
SO  - Int J Oncol. 2005 Apr;26(4):933-43.