Korean J Urol.  2011 Apr;52(4):253-259.

Cyclooxygenase-2 Overexpression in Chronic Inflammation Associated with Benign Prostatic Hyperplasia: Is It Related to Apoptosis and Angiogenesis of Prostate Cancer?

• Kim BH
• Kim CI
• Chang HS
• Choe MS
• Jung HR
• Kim DY
• Park CH

Abstract

PURPOSE
This study was performed to investigate the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis/angiogenesis in inflammatory and noninflammatory benign prostatic hyperplasia (BPH) and prostate cancer (PC).
MATERIALS AND METHODS
This study involved 64 BPH and 57 PC patients. The BPH histopathologies were classified by the presence of chronic inflammation as follows: noninflammatory BPH (NI-BPH; n=23) and inflammatory BPH (I-BPH; n=41). The association between the expression of COX-2, expression of Bcl-2, the apoptotic index (AI), expression of vascular endothelial growth factor (VEGF), and microvascular density (MVD) in the prostate was investigated.
RESULTS
An overexpression of COX-2, Bcl-2, and VEGF was observed in cases of PC compared with cases of BPH. In PC, the AI was lower and MVD was higher than in BPH. In NI-BPH, I-BPH, and PC, the overexpression of COX-2, Bcl-2, and VEGF gradually increased. The AI was high in I-BPH, but did not differ significantly between the NI-BPH and I-BPH groups or between the NI-BPH and PC groups. MVD was significantly high in PC, but no significant difference was found between NI-BPH and I-BPH. A significant correlation was shown between the overexpression of COX-2 and Bcl-2, and COX-2 and VEGF. However, the AI was not correlated with the overexpression of COX-2 or Bcl-2. MVD was correlated with the overexpression of COX-2 and VEGF.
CONCLUSIONS
COX-2 overexpression in PC is correlated with a decrease in apoptosis and an increase in angiogenesis. Chronic inflammation in BPH causes an overexpression of COX-2, which induces the increased expression of Bcl-2 and VEGF. It is likely that chronic inflammation plays a role in the intermediate step of carcinogenesis in the prostate.

Keyword

Angiogenesis-inducing agents; Apoptosis; Cyclooxygenase 2; Prostatic hyperplasia; Prostatic neoplasms

MeSH Terms

Apoptosis
Cyclooxygenase 2
Humans
Inflammation
Prostate
Prostatic Hyperplasia
Prostatic Neoplasms
Vascular Endothelial Growth Factor A
Cyclooxygenase 2
Vascular Endothelial Growth Factor A

Figure

• 

  FIG. 1 Immunohistochemistry analysis of COX-2, Bcl-2, apoptotic index, VEGF, and MVD in PC (A-E) and BPH (F-J). COX-2 (A, F), Bcl-2 (B, G), and VEGF (D, I) were positive in cytoplasm of tumor cells or epithelial cells of BPH. They were more prominent in PC than in BPH. CD34 for MVD was positive in cytoplasm of endothelial cells. MVD was markedly increased in PC (E) compared with BPH (J). TUNEL stain for apoptotic index showed a nuclear pattern. Apoptotic index was lower in PC (C) than in BPH (H). COX-2: cyclooxygenase-2, VEGF: vascular endothelial growth factor, MVD: microvascular density, BPH: benign prostatic hyperplasia, PC: prostate cancer.

• 

  FIG. 2 Apoptotic index in NI-BPH, I-BPH, and PC. Statistical analysis showed a significant increase in the apoptotic index in I-BPH compared with PC (p<0.001). The apoptotic index was also high in I-BPH compared with NI-BPH, but the difference was not significant (p=0.050). NI-BPH: noninflammatory benign prostatic hyperplasia, I-BPH: inflammatory benign prostatic hyperplasia, PC: prostate cancer, a: statistical analysis by Tukey test.

• 

  FIG. 3 MVD in NI-BPH, I-BPH, and PC. Statistical analysis showed a significant increase in MVD in PC compared with NI-BPH and I-BPH (p<0.001). No significant difference was found between NI-BPH and I-BPH (p=0.530). MVD: microvascular density, NI-BPH: noninflammatory benign prostatic hyperplasia, I-BPH: inflammatory benign prostatic hyperplasia, PC: prostate cancer, a: statistical analysis by Tukey's test.

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