PMID- 12095550 OWN - NLM STAT- MEDLINE DCOM- 20020809 LR - 20220317 IS - 0360-3016 (Print) IS - 0360-3016 (Linking) VI - 53 IP - 4 DP - 2002 Jul 15 TI - Expression of hypoxia-inducible factor-1alpha in cervical carcinomas: correlation with tumor oxygenation. PG - 854-61 AB - PURPOSE: To investigate the relations between hypoxia-inducible factor-1 (HIF-1), tumor oxygenation, and clinical correlates in patients with locally advanced carcinoma of the uterine cervix. METHODS AND MATERIALS: Biopsies from 42 patients with invasive cervical carcinoma and previous polarographic O2 measurements were assessed for the expression of HIF-1alpha using digitized microscopic imaging and analysis. RESULTS: The HIF-1alpha expression levels ranged from <0.1% to 10.7% of the total tumor area; the positive staining was localized exclusively to the nuclei. Three distinct arrangement patterns of HIF-1alpha-positive cells in relation to blood vessels were identified using spatial image mapping: (1) most HIF-1alpha-positive cells were located within the typical oxygen diffusion distance in tissue (< or =150 microm to the nearest blood vessel); (2) most HIF-1alpha-positive cells were located in the vicinity (< or =60 microm) of the blood vessels; and (3) no apparent spatial relationship was found between HIF-1alpha-positive cells and blood vessels. A statistically significant association was found between HIF-1alpha expression and tumor oxygenation (Spearman correlation coefficient = 0.4, p <0.01), as determined with the Eppendorf pO2 histograph. No correlation was found between the level of HIF-1alpha expression and patient outcome, using disease-free survival as the end point. CONCLUSION: Our results suggest that HIF-1alpha expression may represent a useful biologic marker for hypoxia in uterine cervical cancer. FAU - Haugland, Hans Kristian AU - Haugland HK AD - Department of Medical Biophysics, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada. FAU - Vukovic, Vojislav AU - Vukovic V FAU - Pintilie, Melania AU - Pintilie M FAU - Fyles, Anthony W AU - Fyles AW FAU - Milosevic, Michael AU - Milosevic M FAU - Hill, Richard P AU - Hill RP FAU - Hedley, David W AU - Hedley DW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Radiat Oncol Biol Phys JT - International journal of radiation oncology, biology, physics JID - 7603616 RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Transcription Factors) RN - S88TT14065 (Oxygen) SB - IM MH - Aged MH - Carcinoma/*metabolism MH - Disease-Free Survival MH - Female MH - Humans MH - Hypoxia MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Image Processing, Computer-Assisted MH - Immunohistochemistry MH - Middle Aged MH - Oxygen/*metabolism MH - Time Factors MH - Transcription Factors/*metabolism MH - Uterine Cervical Neoplasms/*metabolism EDAT- 2002/07/04 10:00 MHDA- 2002/08/10 10:01 CRDT- 2002/07/04 10:00 PHST- 2002/07/04 10:00 [pubmed] PHST- 2002/08/10 10:01 [medline] PHST- 2002/07/04 10:00 [entrez] AID - S0360301602028158 [pii] AID - 10.1016/s0360-3016(02)02815-8 [doi] PST - ppublish SO - Int J Radiat Oncol Biol Phys. 2002 Jul 15;53(4):854-61. doi: 10.1016/s0360-3016(02)02815-8.