PMID- 15185341
OWN - NLM
STAT- MEDLINE
DCOM- 20040720
LR  - 20181130
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 111
IP  - 1
DP  - 2004 Aug 10
TI  - Hypoxia-inducible factor-1 alpha in non small cell lung cancer: relation to 
      growth factor, protease and apoptosis pathways.
PG  - 43-50
AB  - Hypoxia-inducible factor (HIF)-1 alpha is the regulatory subunit of HIF-1 that is 
      stabilized under hypoxic conditions. Under different circumstances, HIF-1 alpha 
      may promote both tumorigenesis and apoptosis. There is conflicting data on the 
      importance of HIF-1 alpha as a prognostic factor. This study evaluated HIF-1 
      alpha expression in 172 consecutive patients with stage I-IIIA non small cell 
      lung cancer (NSCLC) using standard immunohistochemical techniques. The extent of 
      HIF-1 alpha nuclear immunostaining was determined using light microscopy and the 
      results were analyzed using the median (5%) as a low cut-point and 60% as a high 
      positive cut-point. Using the low cut-point, positive associations were found 
      with epidermal growth factor receptor (EGFR; p = 0.01), matrix metalloproteinase 
      (MMP)-9 (p = 0.003), membranous (p < 0.001) and perinuclear (p = 0.004) carbonic 
      anhydrase (CA) IX, p53 (p = 0.008), T-stage (p = 0.042), tumor necrosis (TN; p < 
      0.001) and squamous histology (p < 0.001). No significant association was found 
      with Bcl-2 or either N- or overall TMN stage or prognosis. When the high positive 
      cut-point was used, HIF-1 alpha was associated with a poor prognosis (p = 0.034). 
      In conclusion, the associations with EGFR, MMP-9, p53 and CA IX suggest that 
      these factors may either regulate or be regulated by HIF-1 alpha. The association 
      with TN and squamous-type histology, which is relatively more necrotic than other 
      NSCLC types, reflects the role of hypoxia in the regulation of HIF-1 alpha. The 
      prognostic data may reflect a change in the behavior of HIF-1 alpha in 
      increasingly hypoxic environments.
CI  - Copyright 2004 Wiley-Liss, Inc.
FAU - Swinson, Daniel E B
AU  - Swinson DE
AD  - Cancer Centre, Queen Elizabeth Hospital, Birmingham, United Kingdom. 
      daniel.swinson@fsmail.net
FAU - Jones, J Louise
AU  - Jones JL
FAU - Cox, Giles
AU  - Cox G
FAU - Richardson, Donna
AU  - Richardson D
FAU - Harris, Adrian L
AU  - Harris AL
FAU - O'Byrne, Kenneth J
AU  - O'Byrne KJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apoptosis
MH  - Biomarkers, Tumor
MH  - Carbonic Anhydrases/analysis
MH  - Carcinoma, Non-Small-Cell Lung/*pathology
MH  - Cell Hypoxia
MH  - Cross-Sectional Studies
MH  - ErbB Receptors/analysis
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Immunohistochemistry
MH  - Lung Neoplasms/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 9/analysis
MH  - Middle Aged
MH  - Necrosis
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Transcription Factors/analysis/*biosynthesis
EDAT- 2004/06/09 05:00
MHDA- 2004/07/21 05:00
CRDT- 2004/06/09 05:00
PHST- 2004/06/09 05:00 [pubmed]
PHST- 2004/07/21 05:00 [medline]
PHST- 2004/06/09 05:00 [entrez]
AID - 10.1002/ijc.20052 [doi]
PST - ppublish
SO  - Int J Cancer. 2004 Aug 10;111(1):43-50. doi: 10.1002/ijc.20052.