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Possible Role of HER-2 in the Progression of Prostate Cancer from Primary Tumor to Androgen Independence

  • Murray, Nigel P (Hematology, Medicine, Hospital de Carabineros de Chile, Faculty of Medicine University Finis Terrae) ;
  • Reyes, Eduardo (Faculty of Medicine University Diego Portales, Hospital DIPRECA) ;
  • Fuentealba, Cynthia (Urology, Hospital de Carabineros de Chile) ;
  • Jacob, Omar (Urology, Hospital de Carabineros de Chile) ;
  • Orellana, Nelson (Urology, Hospital de Carabineros de Chile)
  • Published : 2015.10.06

Abstract

Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and Methods: Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest(R), CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest(R) to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. Results: 144 men with a mean age of $64.8{\pm}10.3$ years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.

Keywords

Prostate cancer;HER-2;circulating prostate cells;biochemical failure;castrate resistant

References

  1. Bai Q, Chen F, Qi J, et al (2007). Relationship between HER-2/neu expression and androgen independent prostate cancer. Zhonghua Nan Ke Xue, 13, 414-416
  2. Craft N, Shostak Y, Carey M, et al (1999). A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat Med, 5, 280-5. https://doi.org/10.1038/6495
  3. Guyader C, Ceraline J, Gravier E, et al (2012). Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors. PloS ONE, 7. http://doi.10.1371/journalpone.Oc42252
  4. Fehm T, Mller V, Aktas B, et al (2010). HER-2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective multicentre trial. Breast Cancer Res Treat, 124, 403-12 https://doi.org/10.1007/s10549-010-1163-x
  5. Hudis CA (2007). Trastuzumab--mechanism of action and use in clinical practice. N Engl J Med, 357, 39-51. https://doi.org/10.1056/NEJMra043186
  6. Lara PN, Meyers FJ, Gray CR, et al (2002). Her-2/neu is overexpressed infrequently in patients with prostate carcinoma. Cancer, 94, 2584-9 https://doi.org/10.1002/cncr.10526
  7. Liu HL, Gandour-Edwards R, Lara PN Jr, et al (2001). Detection of low level HER-2/neu gene amplification in prostate cancer by fluorescence in situ hybridization. Cancer J, 7, 395-403.
  8. Montironi R, Mazzucchelli R, Barbisan F, et al.(2006). HER-2 expression and gene amplication in pTa Gleason score 6 prostate cancer incidentally detected in cystoprostatectomy: comparison with clinically detected androgen dependent and androgen independent cancer. Hum Pathol, 37, 1137-44. https://doi.org/10.1016/j.humpath.2006.04.004
  9. Murray NP, Badinez LV, Duenas R, et al (2011). Positive HER- 2 protein expression in circulating prostate cells and micro-metastasis, resistant to androgen blockage but not diethylstilbestrol. Indian J Urol, 27, 200-207. https://doi.org/10.4103/0970-1591.82838
  10. Murray NP, Reyes E, Orellana N, et al (2013). Secondary circulating prostate cell in prostate cancer patients after radical prostatectomy and without evidence of disease predict biochemical failure. TWSJ Urol. http://doi.10.1155/2013/281291
  11. Neto AS, Tobias-Machado M, Wroclawski ML, et al (2010). Her-2/neu expression in prostate adenocarcinoma: a systematic review and meta-analysis. J Urol, 184, 842-50. https://doi.org/10.1016/j.juro.2010.04.077
  12. Osman I, Scher HI, Drobnjak M, et al (2001). HER-2/ neu (p185neu) protein expression in the natural or treated history of prostate cancer. Clin Cancer Res. 7, 2643-7.
  13. Ratan HL, Gescher A, Steward WP, et al (2003). ErbB receptors: possible therapeutic targets in prostate cancer? BJU Int. 92, 890-5. https://doi.org/10.1111/j.1464-410X.2003.04503.x
  14. Rink M, Chun FK, Dahlem R, et al (2012). Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study. Eur Urol, 61, 810-7. https://doi.org/10.1016/j.eururo.2012.01.017
  15. Shariat SF, Bensalah K, Karam JA, et al (2007). Preoperative plasma HER-2 and EGFR for staging and prognostication in patients with clinically localized prostate cancer. Clin Cancer Res, 13, 5377-84 https://doi.org/10.1158/1078-0432.CCR-07-0330
  16. Siampanopoulou M, Galaktidou G, Dimasis N, et al (2013). Profiling serum HER-2/neu in prostate cancer. Hippokratia, 17, 108-112
  17. Signoretti S, Montironi R, Manola J, et al (2000). Her- 2 neu expression and progression toward androgen independence in human prostate cancer. J Natl Cancer Inst, 92, 1918-25. https://doi.org/10.1093/jnci/92.23.1918
  18. Weiss L (1990). Metastatic inefficiency. Adv Cancer Res, 54, 159-211. https://doi.org/10.1016/S0065-230X(08)60811-8
  19. Wen Y, Hu MC, Makino K, et al (2000). HER-2/ neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res, 60, 6841-5.
  20. Yeh S, Lin HK, Kang HY, et al (1999). HER-2/neu signal cascade to androgen receptor and its coactivators: a novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Natl Acad Sci USA, 96, 5458-63. https://doi.org/10.1073/pnas.96.10.5458
  21. Zahir ST, Tafti HF, Rahmani K (2014). Overepression of HER-2/ neu in patients with prostatic adenocarcinoma. Asian Pac J Cancer Prev, 15, 6425-8 https://doi.org/10.7314/APJCP.2014.15.15.6425

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