Co-expression and impact of prostate specific membrane antigen and prostate specific antigen in prostatic pathologies

Abstract

Background: The present study was undertaken to relate the co-expression of prostate-associated antigens, PSMA and PSA, with the degree of vascularization in normal and pathologic (hyperplasia and cancer) prostate tissues to elucidate their possible role in tumor progression.

Methods: The study was carried out in 6 normal, 44 benign prostatic hyperplastic and 39 cancerous human prostates. Immunohistochemical analysis were performed using the monoclonal antibody CD34 to determine the angiogenic activity, and the monoclonal antibodies 3E6 and ER-PR8 to assess PSMA and PSA expression, respectively.

Results: In our study we found that in normal prostate tissue, PSMA and PSA were equally expressed (3.7 ± 0.18 and 3.07 ± 0.11). A significant difference in their expression was see in hyperplastic and neoplastic prostates tissues (16.14 ± 0.17 and 30.72 ± 0.85, respectively) for PSMA and (34.39 ± 0.53 and 17.85 ± 1.21, respectively) for PSA. Study of prostate tumor profiles showed that the profile (PSA+, PSMA-) expression levels decreased between normal prostate, benign prostatic tissue and primary prostate cancer. In the other hand, the profile (PSA-, PSMA+) expression levels increased from normal to prostate tumor tissues. PSMA overexpression was associated with high intratumoral angiogenesis activity. By contrast, high PSA expression was associated with low angiogenesis activity.

Conclusion: These data suggest that these markers are regulated differentially and the difference in their expression showed a correlation with malignant transformation. With regard to the duality PSMA-PSA, this implies the significance of their investigation together in normal and pathologic prostate tissues.

Figure 1

H & E stained slides in NP (B), BPH (F) and PC (J); immunohistochemical localizations of PSMA, PSA and CD34. Negative control (A). NP showing weak cytoplasmic staining for PSMA (C) and PSA (D) in epithelial cells. CD34 was found at low level in membranous and cytoplasmic endothelial cells in NP (E) and BPH (I). BPH showing weak membranous staining for PSMA (G) and strong membranous and cytoplasmic staining for PSA (H) in prostatic epithelial cells. PSMA (K) and CD34 (M) showed strong immunoreactions in infiltrating prostatic carcinoma. PSA (L) showed weak cytoplasmic immunoreactions of epithelial cells in PC. Scale bars: A-G, I-M, 20 μm; H, 30 μm.

Figure 2

Distribution of tissue PSMA (A), PSA (B) and CD34 (C) immunostaining intensity (measured as average optical density) according to normal prostate (NP), benign prostatic hyperplasia (BPH) and prostatic carcinoma (PC). Average optical densities were evaluated only in patients showing immunopositivity.

Figure 3

Association between immunostaining intensity of CD34, PSMA and PSA expression among tissue CD34 levels in benign prostatic hyperplasia (BPH) (A) and prostate cancer (PC) patients (B). Values were expressed as mean ± SEM. Average optical densities were evaluated only in patients showing immunopositivity. Statistical analysis refers to each antibody separately. Values denoted by different superscripts are significantly different from each other. Those values sharing the same superscript are not statistically different from each other. Statistical analysis refers to each antibody separately. Significance was determined at p≤0. 05; 2.34: Mean O.D of CD34 value in NP; 8: Mean O.D of CD34 value in BPH and 12.08: Mean O.D of CD34 value in PC patients.

Figure 4

Percentage of prostatic specimens with positive or negative immunoreactions to PSA and PSMA according to groups: normal prostate (NP), benign prostatic hyperplasia (BPH) and prostatic carcinoma (PC). Statistical analysis refers to each group separately at p≤0.05.

Figure 5

Comparison of the intensity of immunoreactivity (measured as average optical density ± SEM) for PSA and PSMA according to groups: normal prostate (NP), benign prostatic hyperplasia (BPH) and prostatic carcinoma (PC) among (PSA+, PSMA+) profile. Values denoted by different superscripts are significantly different from each other. Those values sharing the same superscript are not statistically different from each other. Statistical analysis refers to each antibody separately. Significance was determined at p≤0. 05.