title: Expression of hypoxia-inducible factor-1alpha protein predicts survival in patients with transitional cell carcinoma of the upper urinary tract.
abstract: Hypoxia-inducible factor-1 (HIF-1), identified as one of the transcription factors, has been found to play an essential role in oxygen homeostasis. HIF-1 is a heterodimer composed of HIF-1alpha and HIF-1beta. Increased levels of HIF-1alpha have been reported during the carcinogenesis and progress of several tumors. We investigated the prognostic importance of HIF-1alpha expression in transitional cell carcinoma of the upper urinary tract. In 127 cases of transitional cell carcinoma of the upper urinary tract, we examined its expression (using immunohistochemistry and in situ hybridization), and also its relation to the expression of p53 oncoprotein, as well as to proliferating cell nuclear antigen (PCNA) immunoreactivity, microvessel density, clinicopathologic parameters, and clinical outcome. A positive expression of HIF-1alpha protein was recognized in 55.1% of samples, the expression being apparent within the nucleus in tumor cells. HIF-1alpha protein expression correlated with grade, growth pattern, p53 oncoprotein expression, and PCNA index, but not with stage. Furthermore, a significant correlation was found between HIF-1alpha protein expression and both overall and disease-free survival rates in the univariate and multivariate analyses (in all tumors and in invasive tumors). A positive expression of HIF-1alpha mRNA was recognized in 69.6% of 125 samples which were available, the expression being apparent within the cytoplasm in tumor cells. The positive expression of HIF-1alpha mRNA by in situ hybridization correlated significantly with HIF-1alpha protein expression by immunohistochemistry. HIF-1alpha mRNA expression only correlated with pattern of growth (P = 0.0078). In conclusion, the detection of HIF-1alpha protein would seem to be of value in informing the prognosis of transitional cell carcinoma of the upper urinary tract.
authors.affiliation: Department of Pathology, National Defense Medical College, Tokorozawa, Japan. nknsknak@res.ndmc.ac.jp
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hiroi
authors.forename: Susumu
authors.initials: S
authors.lastname: Tominaga
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Aida
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kasamatsu
authors.forename: Shigeo
authors.initials: S
authors.lastname: Matsuyama
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014571:Urologic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D014157:Transcription Factors