ABSTRACT
Background: [PSMA+,PSA+] and [PSMA+,PSA-] are the two most individual clones that we have previously identified during prostate cancer [PC] progression. However, molecular signatures associated with these distinct PSMA-PSA prostate clones and their specific correlation with disease outcome is yet to be defined
Aim: Since Akt is a major pathway involved in the critical activating events that leads to malignant form of the disease, we studied the involvement of full Akt activation [T308+,S473+] connected with serum PSA levels, tissue PSMA expression and angiogenic activity on the emergence of [PSMA+,PSA+] and [PSMA+,PSA-] PC clones
Methods: The study was carried out in 6 normal prostate, 25 benign prostate hyperplasia [BPH] and 23 [PC]. Immunohistochemical analysis was performed to study the expression of PSMA, PSA, pAkt[T308], pAkt[S473] and CD34 in prostate tissues. The evaluation of angiogenesis was made by CD34 immune marker. Serum levels of PSA were assayed by Immulite autoanalyser
Results:The most relevant result showed that, among PC patients with pAkt [T308+,S473+] profile, patients that exhibit the [PSMA+,PSA+] clone have higher serum PSA levels, tissue PSMA expression and angiogenic activity than those with [PSMA+,PSA-] clone. Although have the same [PSMA+,PSA+] prostate clone, BPH patients have distinct molecular-biological features compared to PC patients among pAkt [T308+,S473+] profile. In fact, among patients with maximal Akt activation, the [PSMA+,PSA+] PC clone is characterized by higher serum PSA levels, tissue PSMA production and intensive angiogenic activity than [PSMA+,PSA+] BPH clone
Conclusion: These findings emphasize the potential role of the full Akt activation [T308+,S473+] in expansion of several PSMA-PSA prostate clones capable of driving both human PC initiation as well as progression to a metastatic phenotype. Pinpoint patients according to PSMA-PSA clones could recapitulate the histological and molecular features of human PC and may offer a novel approach for controlling metastasis
ABSTRACT
As promising targets for in vivo diagnostic, prognostic and therapeutic approaches, the distribution and staining pattern of prostate specific antigen [PSA] and prostate specific membrane antigen [PSMA] in tumors are of significant interest. To compare the cellular distribution and heterogeneity of PSA and PSMA expression in normal prostate [NP], benign prostatic hyperplasia [BPH] and primary prostatic tumors and to analyze their relation with the angiogenic activity according to Gleason grade [low, medium and high] in primary PC. The study was carried out in 6 NP, 44 BPH and 39 PC. Immunohistochemical analysis was performed. Monoclonal antibodies 3E6 and ER-PR8 were used to assess PSMA and PSA expression respectively. The evaluation of angiogenesis was made by CD34 immune marker. In our study we noticed differences in the intracellular localization of the PSMA immunostaining which seem to be related to the normal and pathological context. A significant number of primary tumors presented with apical pattern of PSMA [28/39]; whereas a relevant part of NP samples and BPH samples showed cytoplasmic localization [4/6 and 30/44, respectively] in luminal epithelial cells. Compared to PSMA, PSA was preferentially localized in cytoplasmic compartment in all type of prostate. A direct correlation between histological grade, PSMA expression and angiogenic activity could be demonstrated in primary PC. Simultaneous stains with PSA and PSMA in individual prostate tissue will greatly improve the detection rate and identify a high risk PC that could progress to metastatic phenotype. Our findings clearly support the feasibility but also direct the potential of PSMA-targeted in vivo therapeutic approaches in PC patients rather than PSA especially those with poorly differentiated adenocarcinoma