Cellular distribution and heterogeneity of Psa and Psma expression in normal, hyperplasia and human prostate cancer

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Published Aug 21, 2013
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Vol. 91 No. 7 (2013): Issue Jul 2013

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Awatef Ben Jemaa
Yosra Bouraoui
Sataa Sallami
Ahmed Banasr
Yassine Nouira
Ali Horchani
Ridha Oueslati

Abstract

Background: 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.
aims: 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.
methods: 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.
results: 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.
Conclusions: 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.

Keywords:

PSA, PSMA, staining pattern, Gleason score, angiogenic activity

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References

  1. Williams SA, Singh P, Isaacs JT, Denmeade SR. Does PSA play a role as a promoting agent during the initiation andor progression of prostate cancer? Prostate. 2007; 67:312-29.
  2. Rajasekaran AK, Anilkumar G, Christiansen JJ. Is prostate-specific membrane antigen a multifunctional protein? Am J Physiol Cell Physiol. 2005; 288: C975-C981.
  3. Lilja H. Structure, function and regulation of the enzyme activity of prostate-specific antigen. World J Urol. 1993; 11:188-91.
  4. Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: Structure, function, and association to disease. Endocr Rev. 2001, 22:184-204.
  5. Roscigno M, Scattoni V, Bertini R, Pasta A, Montorsi F, Rigatti P. Diagnosis of prostate cancer. State of the art. Minerva Urol Nefrol. 2004 ; 56:123-45.
  6. Bouraoui Y, Ben Rais N, Elouni Z, Mezigh C, Machghoul S, Oueslati R. Evolution's molecular forms of Prostate-Specific- Antigen in serological groups of patients with prostatic pathologies. Immunobio. 2006; 21 :286-91.
  7. Klyushnenkova EN, Kouiavskaia DV, Parkins CJ, et al. A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer. J Immunother. 2012 ; 35:390-99.
  8. Chang SS. Overview of prostate-specific membrane antigen. Rev Urol Suppl. 2004: 10; S13-S18.
  9. Pinto JT, Suffoletto BP, Berzin TM, et al. Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. Clin Cancer Res. 1996; 2:1445- 51.
  10. Zhang L, Wang CY, Yang R, et al. Real-time quantitative RT-PCR assay of prostate- specific antigen and prostate-specific membrane antigen in peripheral blood for detection of prostate cancer micrometastasis. Urol Oncol. 2008; 26:634-40.
  11. Grant CL, Caromile LA, Durrani K, et al. Prostate Specific Membrane Antigen (PSMA) Regulates Angiogenesis Independently of VEGF during Ocular Neovascularization. PLoS One. 2012 ;7:e41285.
  12. Perner S, Hofer MD, Kim R, et al. Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol. 2007; 38:696-701.
  13. Taylor RM, Sillerud LO. Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner. Int J Nanomedicine. 2012;7:4341-52.
  14. Santana SM, Liu H, Bander NH, Gleghorn JP, Kirby BJ. Immunocapture of prostate cancer cells by use of anti-PSMA antibodies in microdevices. Biomed Microdevices. 2012; 14:401-7.
  15. Mhawech-Fauceglia P, Zhang S, Terracciano L, et al. Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using mutiple tumour tissue microarray technique. Histopathology. 2007;50:472-83.
  16. Schülke N, Varlamova OA, Donovan GP, et al. The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy. Proc Natl Acad Sci U S A, 2003 ; 100:12590-95.
  17. Mlcochová P, Barinka C, Tykvart J, Sácha P, Konvalinka J. Prostate-specific membrane antigen and its truncated form PSM'. Prostate. 2009; 69:471-79.
  18. Aihara M, Lebovitz RM, Wheeler TM, Kinner BM, Ohori M, Scardino PT. Prostate specific antigen and gleason grade: an immunohistochemical study of prostate cancer. J Urol. 1994;151: 1558-64.
  19. Kawakami M, Nakayama J. Enhanced expression of prostatespecific membrane antigen gene in prostate cancer as revealed by in situ hybridization. Cancer Res. 1997;57:2321-24.
  20. Wright Jr GL, Grob BM, Haley C, et al. Upregulation of prostatespecific membrane antigen after androgen-deprivation therapy. Urology. 1996; 48:326-34.
  21. Yin M, Dhir R, Parwani AV. Diagnostic utility of p501s (prostein) in comparison to prostate specific antigen (PSA) for the detection of metastatic prostatic adenocarcinoma. Diagn Pathol. 2007; 2:41.
  22. Fortier AH, Holaday JW, Liang H, et al. Recombinant prostate specific antigen inhibits angiogenesis in vitro and in vivo. Prostate. 2003; 56: 212-19.
  23. Papadopoulos I, Sivridis E, Giatromanolaki A, Koukourakis MI. Tumor angiogenesis is associated with MUC1 overexpression and loss of prostate-specific antigen expression in prostate cancer. Clin Cancer Res. 2001;7: 1533-38.
  24. Conway RE, Petrovic N, Li Z, Heston W, Wu D, Shapiro LH. Prostate-specific membrane antigen regulates angiogenesis by modulating integrin signal transduction. Mol Cell Biol. 2006; 26: 5310-24.
  25. Yao V, Parwani A, Maier C, Heston WDW, Bacich DJ. Moderate Expression of Prostate Specific Membrane Antigen, a Tissue Differentiation Antigen and Folate Hydrolase, Facilitates Prostate Carcinogenesis. Cancer Res. 2008; 68: 9070-77.