Abstract

Vascular endothelial growth factor (VEGF) expression was examined by immunohistochemistry in 45 prostatic carcinoma specimens and ten benign prostatic tumours (BPH). The majority of carcinoma specimens exhibited cytoplasmic staining for VEGF and showed a trend of increasing expression with dedifferentiation (2p = 0.003). Immunoreactive VEGF was also seen in the prostatic carcinoma cell lines, the order of staining intensity was PC3 > DU145 > LNCaP. Intense granular cytoplasmic staining for VEGF was observed in neuroendocrine-like cells which were seen focally in many of the prostatic specimens. Consecutive sections were incubated with a chromogranin A antibody to confirm the neuroendocrine phenotype of these cells. A significant correlation (P < 0.0001) between the total number of intensely stained VEGF-positive cells and chromogranin A-positive cells was found. A subpopulation of neuroendocrine-like cells also showed intense immunoreactivity for transforming growth factor alpha (TGF-alpha). A correlation was observed (2p = 0.0092) between the intensity of VEGF and TGF-alpha immunostaining in carcinoma cells which were not of neuroendocrine differentiation. The presence of these two angiogenic factors may aid the neovascularisation of carcinomas and their increased expression in tumour-associated neuroendocrine cells may contribute to a more aggressive phenotype.

Highlights

  • Vascular endothelial growth factor (VEGF) immunoassays Diffuse cytoplasmic staining of 0 to 1 + intensity was observed in benign prostatic hyperplasia (BPH) secretory epithelium with intense staining of occasional neuroendocrine-like cells within the glandular structures

  • The majority of carcinoma specimens exhibited cytoplasmic staining for this growth factor which showed a trend of increasing VEGF expression with dedifferentiation (Figure 1) (2p = 0.003)

  • This result was similar to that seen for TGF-oa cytoplasmic staining in the consecutive sections (Figure 1) (2p = 0.0349)

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Summary

Methods

Prostate tissue was obtained from 45 patients with histologically diagnosed prostatic carcinoma and ten patients with benign prostatic hyperplasia (BPH). Forty-four of the patients with carcinoma and nine of the patients with BPH underwent transurethral resection (TURP) of their tumours, while the remaining two patients had open prostatectomy operations. A representative sample of the curettings from the operations was fixed in formal saline followed by paraffin wax embedding for subsequent histopathological examination and the VEGF, chromogranin A and TGF-c immunohistochemical assays. For use in immunocytochemical analysis the cells were seeded onto sterile TESPA (3-aminopropyl-triethoxy-silane; Sigma Chemical Co., Dorset, UK) coated coverslips in tissue culture dishes. After 72 h in culture (i.e. still in logarithmic growth) the monolayers were washed in unsupplemented medium and fixed in formal saline (10 min at room temperature), transferred to 70% ethanol (2 x 5 min) and to phosphate-buffered saline (PBS)

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Discussion
Conclusion

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