Usefulness of hypoxia inducible factor-1 alpha in evaluating the prostatic adenocarcinoma viability following neoadjuvant hormone therapy

Cancer Detect Prev. 2007;31(5):396-401. doi: 10.1016/j.cdp.2007.10.007. Epub 2007 Nov 26.

Abstract

Background: In prostatic adenocarcinomas (PAs), the androgen up-regulates hypoxia inducible factor-1 alpha (HIF-1 alpha). It has been reported that the regulation of HIF-1 alpha would become a therapeutic strategy for PAs. This study was designed to elucidate whether or not HIF-1 alpha expression would be associated with PA recurrence after neoadjuvant hormone therapy (NHT).

Methods: The 50 radical prostatectomy specimens after NHT were examined as well as needle biopsy specimens before NHT using immunohistochemistry for HIF-1 alpha.

Results: The therapeutic effects of 50 cases with NHT were assessed as good (20 cases) or poor (30 cases). The recurrence of PA monitored by the serum prostatic specific antigen (PSA) levels occurred in 21 cases (42%). The hypoxic status was evaluated to be divided into two categories: weak (16 cases) or strong (34 cases). The recurrence ratio was 30% (6/20) of cases with good response and 50% (15/30) of cases with poor response (p<0.05). HIF-1 alpha expression profiles were as follows: recurrent cases, weak, 19% (4/21); strong, 81% (17/21) (p<0.05); and non-recurrent cases, weak, 41% (12/29); strong, 59% (17/29) (NS). Compared to PAs with weak HIF-1 alpha expression, PAs with strong HIF-1 alpha expression showed higher PSA levels (12.1 ng/mL vs. 25.0 ng/mL, p<0.05).

Conclusion: HIF-1 alpha is expected to be useful for detection of the viability of PAs after NHT and also for prediction of their clinical outcome. In addition, the expression may contribute to histological identification of the carcinoma cells.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antineoplastic Agents
  • Biomarkers, Tumor / analysis*
  • Cell Survival / drug effects
  • Hormone Antagonists / therapeutic use*
  • Humans
  • Hypoxia-Inducible Factor 1 / biosynthesis*
  • Immunohistochemistry
  • Male
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / pathology
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Hormone Antagonists
  • Hypoxia-Inducible Factor 1
  • Prostate-Specific Antigen