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High placenta-specific 1/low prostate-specific antigen expression pattern in high-grade prostate adenocarcinoma

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Abstract

Background

The scarcity of effective therapeutic approaches for prostate cancer (PCa) has encouraged steadily growing interest for the identification of novel antigenic targets. Placenta-specific 1 (PLAC1) is a novel cancer–testis antigen with reported ectopic expression in a variety of tumors and cancer cell lines. The purpose of the present study was to investigate for the first time the differential expression of PLAC1 in PCa tissues.

Methods

We investigated the differential expression of PLAC1 in PCa, high-grade prostatic intraepithelial neoplasia (HPIN), benign prostatic hyperplasia (BPH), and nonneoplastic/nonhyperplastic prostate tissues using microarray-based immunohistochemistry (n = 227). The correlation of PLAC1 expression with certain clinicopathological parameters and expression of prostate-specific antigen (PSA), as a prostate epithelial cell differentiation marker, were investigated.

Results

Placenta-specific 1 (PLAC1) expression was increased in a stepwise manner from BPH to PCa, which expressed highest levels of this molecule, while in a majority of normal tissues, PLAC1 expression was not detected. Moreover, PLAC1 expression was positively associated with Gleason score (p ≤ 0.001). Interestingly, there was a negative correlation between PLAC1 and PSA expression in patients with PCa and HPIN (p ≤ 0.01). Increment of PLAC1 expression increased the odds of PCa and HPIN diagnosis (OR 49.45, 95 % CI for OR 16.17–151.25).

Conclusion

Our findings on differential expression of PLAC1 in PCa plus its positive association with Gleason score and negative correlation with PSA expression highlight the potential usefulness of PLAC1 for targeted PC therapy especially for patients with advanced disease.

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Abbreviations

BPH:

Benign prostatic hyperplasia

CI:

Confidence interval

DAB:

Diaminobenzidine

HPIN:

High-grade prostatic intraepithelial neoplasia

IHC:

Immunohistochemistry

OR:

Odds ratio

PAP:

Prostate acid phosphatase

PCa:

Prostate cancer

PLAC1:

Placenta-specific 1

PSA:

Prostate-specific antigen

TMA:

Tissue microarray

TRUS:

Transrectal ultrasound

References

  1. Slovin SR (2012) Toward maximizing immunotherapy in metastatic castration-resistant prostate cancer–rationale for combinatorial approaches using chemotherapy. Front Oncol 2:43

    Article  PubMed Central  PubMed  Google Scholar 

  2. Agarwal N, Sonpavde G, Sternberg CN (2012) Novel molecular targets for the therapy of castration-resistant prostate cancer. Eur Urol 61:950–960

    Article  CAS  PubMed  Google Scholar 

  3. Di Lorenzo G, Buonerba C, Kantoff PW (2011) Immunotherapy for the treatment of prostate cancer. Nat Rev Clin Oncol 8:551–561

    Article  PubMed  Google Scholar 

  4. Lang SH, Frame FM, Collins AT (2009) Prostate cancer stem cells. J Pathol 217:299–306

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951

    Article  CAS  PubMed  Google Scholar 

  6. Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG (2006) Highly purified CD44 + prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25:1696–1708

    Article  CAS  PubMed  Google Scholar 

  7. Patrawala L, Calhoun-Davis T, Schneider-Broussard R, Tang DG (2007) Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44 + alpha2beta1 + cell population is enriched in tumor-initiating cells. Cancer Res 67:6796–6805

    Article  CAS  PubMed  Google Scholar 

  8. Pfeiffer MJ, Schalken JA (2010) Stem cell characteristics in prostate cancer cell lines. Eur Urol 57:246–254

    Article  CAS  PubMed  Google Scholar 

  9. Abrahamsson PA, Lilja H, Falkmer S, Wadstrom LB (1988) Immunohistochemical distribution of the three predominant secretory proteins in the parenchyma of hyperplastic and neoplastic prostate glands. Prostate 12:39–46

    Article  CAS  PubMed  Google Scholar 

  10. Feiner HD, Gonzalez R (1986) Carcinoma of the prostate with atypical immunohistological features: clinical and histologic correlates. Am J Surg Pathol 10:765–770

    Article  CAS  PubMed  Google Scholar 

  11. Gallee MP, Visser-de Jong E, van der Korput JA, van der Kwast TH, ten Kate FJ, Schroeder FH, Trapman J (1990) Variation of prostate-specific antigen expression in different tumour growth patterns present in prostatectomy specimens. Urol Res 18:181–187

    Article  CAS  PubMed  Google Scholar 

  12. Qin J, Liu X, Laffin B, Chen X, Choy G, Jeter CR, Calhoun-Davis T, Li H, Palapattu GS, Pang S, Lin K, Huang J, Ivanov I, Li W, Suraneni MV, Tang DG (2012) The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 10:556–569

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Madu CO, Lu Y (2010) Novel diagnostic biomarkers for prostate cancer. J Cancer 1:150–177

    Article  PubMed Central  PubMed  Google Scholar 

  14. Cocchia M, Huber R, Pantano S, Chen EY, Ma P, Forabosco A, Ko MS, Schlessinger D (2000) PLAC1, an Xq26 gene with placenta-specific expression. Genomics 68:305–312

    Article  CAS  PubMed  Google Scholar 

  15. Fant M, Farina A, Nagaraja R, Schlessinger D (2010) PLAC1 (Placenta-specific 1): a novel, X-linked gene with roles in reproductive and cancer biology. Prenat Diagn 30:497–502

    CAS  PubMed  Google Scholar 

  16. Silva WA Jr, Gnjatic S, Ritter E, Chua R, Cohen T, Hsu M, Jungbluth AA, Altorki NK, Chen YT, Old LJ, Simpson AJ, Caballero OL (2007) PLAC1, a trophoblast-specific cell surface protein, is expressed in a range of human tumors and elicits spontaneous antibody responses. Cancer Immun 7:18

    PubMed Central  PubMed  Google Scholar 

  17. Fant M, Weisoly DL, Cocchia M, Huber R, Khan S, Lunt T, Schlessinger D (2002) PLAC1, a trophoblast-specific gene, is expressed throughout pregnancy in the human placenta and modulated by keratinocyte growth factor. Mol Reprod Dev 63:430–436

    Article  CAS  PubMed  Google Scholar 

  18. Massabbal E, Parveen S, Weisoly DL, Nelson DM, Smith SD, Fant M (2005) PLAC1 expression increases during trophoblast differentiation: evidence for regulatory interactions with the fibroblast growth factor-7 (FGF-7) axis. Mol Reprod Dev 71:299–304

    Article  CAS  PubMed  Google Scholar 

  19. Koslowski M, Sahin U, Mitnacht-Kraus R, Seitz G, Huber C, Tureci O (2007) A placenta-specific gene ectopically activated in many human cancers is essentially involved in malignant cell processes. Cancer Res 67:9528–9534

    Article  CAS  PubMed  Google Scholar 

  20. Jackman SM, Kong X, Fant ME (2012) Plac1 (placenta-specific 1) is essential for normal placental and embryonic development. Mol Reprod Dev 79:564–572

    Article  CAS  PubMed  Google Scholar 

  21. Chen J, Pang XW, Liu FF, Dong XY, Wang HC, Wang S, Zhang Y, Chen WF (2006) PLAC1/CP1 gene expression and autologous humoral immunity in gastric cancer patients. Beijing Da Xue Xue Bao 38:124–127

    CAS  PubMed  Google Scholar 

  22. Dong XY, Peng JR, Ye YJ, Chen HS, Zhang LJ, Pang XW, Li Y, Zhang Y, Wang S, Fant ME, Yin YH, Chen WF (2008) Plac1 is a tumor-specific antigen capable of eliciting spontaneous antibody responses in human cancer patients. Int J Cancer 122:2038–2043

    Article  CAS  PubMed  Google Scholar 

  23. Tchabo NE, Mhawech-Fauceglia P, Caballero OL, Villella J, Beck AF, Miliotto AJ, Liao J, Andrews C, Lele S, Old LJ, Odunsi K (2009) Expression and serum immunoreactivity of developmentally restricted differentiation antigens in epithelial ovarian cancer. Cancer Immun 9:6

    PubMed Central  PubMed  Google Scholar 

  24. Ghods R, Ghahremani MH, Darzi M, Mahmoudi AR, Yeganeh O, Bayat AA, Pasalar P, Jeddi-Tehrani M, Zarnani AH (2014) Immunohistochemical characterization of novel murine monoclonal antibodies against human placenta-specific 1. Biotechnol Appl Biochem 61:363–369

    CAS  PubMed  Google Scholar 

  25. Epstein JI, Allsbrook WC, Amin MB, Egevad LL (2005) The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 29:1228–1242

    Article  PubMed  Google Scholar 

  26. Cheng L, Montironi R, Bostwick DG, Lopez-Beltran A, Berney DM (2012) Staging of prostate cancer. Histopathology 60:87–117

    Article  PubMed  Google Scholar 

  27. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847

    Article  CAS  PubMed  Google Scholar 

  28. Mohsenzadegan M, Madjd Z, Asgari M, Abolhasani M, Shekarabi M, Taeb J, Shariftabrizi A (2013) Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis. Cancer Immunol Immunother 62:1609–1618

    Article  CAS  PubMed  Google Scholar 

  29. Mahmoudi AR, Zarnani AH, Jeddi-Tehrani M, Katouzian L, Tavakoli M, Soltanghoraei H, Mirzadegan E (2013) Distribution of vitamin D receptor and 1alpha-hydroxylase in male mouse reproductive tract. Reprod Sci 20:426–436

    Article  CAS  PubMed  Google Scholar 

  30. Zarnani AH, Shahbazi M, Salek-Moghaddam A, Zareie M, Tavakoli M, Ghasemi J, Rezania S, Moravej A, Torkabadi E, Rabbani H, Jeddi-Tehrani M (2010) Vitamin D3 receptor is expressed in the endometrium of cycling mice throughout the estrous cycle. Fertil Steril 93:2738–2743

    Article  CAS  PubMed  Google Scholar 

  31. Barry MJ (2001) Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. N Engl J Med 344:1373–1377

    Article  CAS  PubMed  Google Scholar 

  32. Chen Y, Schlessinger D, Nagaraja R (2013) T antigen transformation reveals Tp53/RB-dependent route to PLAC1 transcription activation in primary fibroblasts. Oncogenesis 2:e67. doi:10.1038/oncsis.2013.31

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Eastham JA, Stapleton AM, Gousse AE, Timme TL, Yang G, Slawin KM, Wheeler TM, Scardino PT, Thompson TC (1995) Association of p53 mutations with metastatic prostate cancer. Clin Cancer Res 1:1111–1118

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by grants from Iran University of Medical Sciences (Grant No: 92-02-13-22395), and Tehran University of Medical Sciences (Grant No: 90-03-13-13530). The authors would like to thank Dr M. Bozorgmehr for carefully proofreading the manuscript, Mr. E. Mirzadegan for technical assistance and preparation of figures, and Mrs. J. Taeb for arranging clinicopathological data.

Conflict of interest

All authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, School of Advanced Medical Technologies, Tehran University of Medical Sciences, TUMS, Tehran, Iran

    Roya Ghods, Mohammad-Hossein Ghahremani & Parvin Pasalar

  2. Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Roya Ghods, Ahmad-Reza Mahmoudi, Maryam Darzi & Mahmood Jeddi-Tehrani

  3. Department of Pharmacology-Toxicology, Faculty of Medicine, Tehran University of Medical Sciences, TUMS, Tehran, Iran

    Mohammad-Hossein Ghahremani

  4. Oncopathology Research Center, Iran University of Medical Sciences, IUMS, Tehran, Iran

    Zahra Madjd, Mojgan Asgari & Maryam Abolhasani

  5. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, IUMS, Tehran, Iran

    Zahra Madjd

  6. Department of Pathology, Hasheminejad Kidney Center, Iran University of Medical Sciences, IUMS, Tehran, Iran

    Mojgan Asgari & Maryam Abolhasani

  7. Department of Nutrition, Science and Research Branch, Azad University, Tehran, Iran

    Sanaz Tavasoli

  8. Immunology Research Center, Iran University of Medical Sciences, IUMS, Hemmat Highway, P.O. box: 1449614535, Tehran, Iran

    Amir-Hassan Zarnani

  9. Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Amir-Hassan Zarnani

  10. School of Advanced Technologies in Medicine, Eastern side of Tehran University, 88, Italia St, P.O. box: 1417755469, Tehran, Iran

    Mohammad-Hossein Ghahremani

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  1. Roya Ghods
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Corresponding authors

Correspondence to Mohammad-Hossein Ghahremani or Amir-Hassan Zarnani.

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Ghods, R., Ghahremani, MH., Madjd, Z. et al. High placenta-specific 1/low prostate-specific antigen expression pattern in high-grade prostate adenocarcinoma. Cancer Immunol Immunother 63, 1319–1327 (2014). https://doi.org/10.1007/s00262-014-1594-z

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  • DOI: https://doi.org/10.1007/s00262-014-1594-z

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