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Molecular prognostic factors in penile cancer

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Abstract

Objectives

Penile cancer is a rare tumour in developed countries but more common in South America and East Africa. Although pathological prognostic factors have been established, there is great interest in evaluating molecular markers which correlate with prognosis and outcome.

Methods

We have reviewed the current status of our understanding of the molecular biology of penile cancer in order to identify established and potential prognostic factors in penile cancer. We have conducted an extensive literature search to review the current understanding of the role of prognostic markers in penile cancer.

Results

Although several markers have been evaluated, currently the clinical application of these markers is limited. HPV positive tumours show a variable prognostic outcome. P53 status may correlate with survival in T1 disease but further studies are required to establish the link to lymph node spread.

Conclusions

Pathological variables are well-established but further work is required to investigate the role of molecular markers. The development of molecular prognostic markers is important for the surveillance of patients and prediction of lymph node involvement as well as a prognostic marker for survival.

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References

  1. Burgers JK, Badalament RA, Drago JR (1992) Penile cancer. Clinical presentation, diagnosis, and staging. Urol Clin North Am 19(2):247–256

    PubMed  CAS  Google Scholar 

  2. Pietrzak P, Hadway P, Corbishley CM, Watkin NA (2006) Is the association between balanitis xerotica obliterans and penile carcinoma underestimated? BJU Int 98(1):74–76

    Article  PubMed  Google Scholar 

  3. Castellsague X, Bosch FX, Munoz N, Meijer CJ, Shah KV, de Sanjose S et al (2002) Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med 346(15):1105–1112

    Article  PubMed  Google Scholar 

  4. Franceschi S, Castellsague X, Dal Maso L, Smith JS, Plummer M, Ngelangel C et al (2002) Prevalence and determinants of human papillomavirus genital infection in men. Br J Cancer 86(5):705–711

    Article  PubMed  CAS  Google Scholar 

  5. Lopes A, Hidalgo GS, Kowalski LP, Torloni H, Rossi BM, Fonseca FP (1996) Prognostic factors in carcinoma of the penis: multivariate analysis of 145 patients treated with amputation and lymphadenectomy. J Urol 156(5):1637–1642

    Article  PubMed  CAS  Google Scholar 

  6. Ficarra V, Zattoni F, Artibani W, Fandella A, Martignoni G, Novara G et al (2006) Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis. J Urol 175(5):1700–1704

    Article  PubMed  Google Scholar 

  7. Rubin MA, Kleter B, Zhou M, Ayala G, Cubilla AL, Quint WG et al (2001) Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol 159(4):1211–1218

    PubMed  CAS  Google Scholar 

  8. Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA et al (2005) Penile cancer: importance of circumcision, human papillomavirus and smoking in in situ and invasive disease. Int J Cancer 116(4):606–616

    Article  PubMed  CAS  Google Scholar 

  9. Picconi MA, Eijan AM, Distefano AL, Pueyo S, Alonio LV, Gorostidi S et al (2000) Human papillomavirus (HPV) DNA in penile carcinomas in Argentina: analysis of primary tumors and lymph nodes. J Med Virol 61(1):65–69

    Article  PubMed  CAS  Google Scholar 

  10. Senba M, Kumatori A, Fujita S, Jutavijittum P, Yousukh A, Moriuchi T et al (2006) The prevalence of human papillomavirus genotypes in penile cancers from northern Thailand. J Med Virol 78(10):1341–1346

    Article  PubMed  CAS  Google Scholar 

  11. Gross G, Pfister H (2004) Role of human papillomavirus in penile cancer, penile intraepithelial squamous cell neoplasias and in genital warts. Med Microbiol Immunol 193(1):35–44

    Article  PubMed  CAS  Google Scholar 

  12. Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli-Martins CM et al (2006) Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 367(9518):1247–1255

    Article  PubMed  CAS  Google Scholar 

  13. Heideman DA, Waterboer T, Pawlita M, Delis-van Diemen P, Nindl I, Leijte JA et al (2007) Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma. J Clin Oncol 25(29):4550–4556

    Article  PubMed  Google Scholar 

  14. zur Hausen H (2002) Papillomavirus and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350

    Article  PubMed  CAS  Google Scholar 

  15. Snijders PJ, van den Brule AJ, Meijer CJ (2003) The clinical relevance of human papillomavirus testing: relationship between analytical and clinical sensitivity. J Pathol 201(1):1–6

    Article  PubMed  Google Scholar 

  16. Bezerra AL, Lopes A, Santiago GH, Ribeiro KC, Latorre MR, Villa LL (2001) Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer 91(12):2315–2321

    Article  PubMed  CAS  Google Scholar 

  17. Wiener JS, Effert PJ, Humphrey PA, Yu L, Liu ET, Walther PJ (1992) Prevalence of human papillomavirus types 16 and 18 in squamous-cell carcinoma of the penis: a retrospective analysis of primary and metastatic lesions by differential polymerase chain reaction. Int J Cancer 50(5):694–701

    Article  PubMed  CAS  Google Scholar 

  18. Lont AP, Kroon BK, Horenblas S, Gallee MP, Berkhof J, Meijer CJ et al (2006) Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival. Int J Cancer 119(5):1078–1081

    Article  PubMed  CAS  Google Scholar 

  19. Ornellas AA, Ornellas MH, Otero L, Simoes F, Campos MM, Harab RC et al (1999) Karyotypic findings in two cases of moderately differentiated squamous cell carcinomas of the penis. Cancer Genet Cytogenet 115(1):77–79

    Article  PubMed  CAS  Google Scholar 

  20. Ornellas AA, Ornellas MH, Simoes F, Soares R, Campos MM, Harab RC et al (1998) Cytogenetic analysis of an invasive, poorly differentiated squamous cell carcinoma of the penis. Cancer Genet Cytogenet 101(1):78–79

    Article  PubMed  CAS  Google Scholar 

  21. Alves G, Heller A, Fiedler W, Campos MM, Claussen U, Ornellas AA et al (2001) Genetic imbalances in 26 cases of penile squamous cell carcinoma. Genes Chromosomes Cancer 31(1):48–53

    Article  PubMed  CAS  Google Scholar 

  22. Hall MC, Sanders JS, Vuitch F, Ramirez E, Pettaway CA (1998) Deoxyribonucleic acid flow cytometry and traditional pathologic variables in invasive penile carcinoma: assessment of prognostic significance. Urology 52(1):111–116

    Article  PubMed  CAS  Google Scholar 

  23. Masih AS, Stoler MH, Farrow GM, Wooldridge TN, Johansson SL (1992) Penile verrucous carcinoma: a clinicopathologic, human papillomavirus typing and flow cytometric analysis. Mod Pathol 5(1):48–55

    PubMed  CAS  Google Scholar 

  24. Ornellas AA, Mendes CM, Ornellas MH, Wisnescky A, Koifman N, Cabral HR (2000) Penile cancer: flow cytometry study of ploidies in 90 patients. Prog Urol 10(1):72–77

    PubMed  CAS  Google Scholar 

  25. Alves G, Fiedler W, Guenther E, Nascimento P, Campos MM, Ornellas AA (2001) Determination of telomerase activity in squamous cell carcinoma of the penis. Int J Oncol 18(1):67–70

    PubMed  CAS  Google Scholar 

  26. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253(5015):49–53

    Article  PubMed  CAS  Google Scholar 

  27. Lopes A, Bezerra AL, Pinto CA, Serrano SV, de MellO CA, Villa LL (2002) p53 as a new prognostic factor for lymph node metastasis in penile carcinoma: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. J Urol 168(1):81–86

    Article  PubMed  Google Scholar 

  28. Lam KY, Chan KW (1999) Molecular pathology and clinicopathologic features of penile tumors: with special reference to analyses of p21 and p53 expression and unusual histologic features. Arch Pathol Lab Med 123(10):895–904

    PubMed  CAS  Google Scholar 

  29. Humbey O, Cairey-Remonnay S, Guerrini JS, Algros MP, Mougin C, Bittard H et al (2003) Detection of the human papillomavirus and analysis of the TP53 polymorphism of exon 4 at codon 72 in penile squamous cell carcinomas. Eur J Cancer 39(5):684–690

    Article  PubMed  CAS  Google Scholar 

  30. Pilotti S, Donghi R, D’Amato L, Giarola M, Longoni A, Della TG et al (1993) HPV detection and p53 alteration in squamous cell verrucous malignancies of the lower genital tract. Diagn Mol Pathol 2(4):248–256

    PubMed  CAS  Google Scholar 

  31. Levi JE, Rahal P, Sarkis AS, Villa L (1998) Human papillomavirus DNA and p53 status in penile carcinomas. Int J Cancer 76(6):779–783

    Article  PubMed  CAS  Google Scholar 

  32. Camus S, Menendez S, Cheok CF, Stevenson LF, Lain S, Lane DP (2007) Ubiquitin-independent degradation of p53 mediated by high-risk human papillomavirus protein E6. Oncogene 26(28):4059–4070

    Article  PubMed  CAS  Google Scholar 

  33. Martins AC, Faria SM, Cologna AJ, Suaid HJ, Tucci S Jr (2002) Immunoexpression of p53 protein and proliferating cell nuclear antigen in penile carcinoma. J Urol 167(1):89–92

    Article  PubMed  CAS  Google Scholar 

  34. Zhu Y, Zhou XY, Yao XD, Dai B, Ye DW (2007) The prognostic significance of p53, Ki-67, epithelial cadherin and matrix metalloproteinase-9 in penile squamous cell carcinoma treated with surgery. BJU Int 100(1):204–208

    Article  PubMed  CAS  Google Scholar 

  35. Prowse DM, Ktori EN, Chandrasekaran D, Prapa A, Baithun S (2008) Human papillomavirus-associated increase in p16(INK4A) expression in penile lichen sclerosus and squamous cell carcinoma. Br J Dermatol 158(2):261–265

    Article  PubMed  CAS  Google Scholar 

  36. Ferreux E, Lont AP, Horenblas S, Gallee MP, Raaphorst FM, von Knebel DM et al (2003) Evidence for at least three alternative mechanisms targeting the p16INK4A/cyclin D/Rb pathway in penile carcinoma, one of which is mediated by high-risk human papillomavirus. J Pathol 201(1):109–118

    Article  PubMed  CAS  Google Scholar 

  37. Senekjian EK, Young JM, Weiser PA, Spencer CE, Magic SE, Herbst AL (1987) An evaluation of squamous cell carcinoma antigen in patients with cervical squamous cell carcinoma. Am J Obstet Gynecol 157(2):433–439

    PubMed  CAS  Google Scholar 

  38. Mino N, Iio A, Hamamoto K (1988) Availability of tumor-antigen 4 as a marker of squamous cell carcinoma of the lung and other organs. Cancer 62(4):730–734

    Article  PubMed  CAS  Google Scholar 

  39. Wishnow KI, Johnson DE, Fritsche H (1990) Squamous cell carcinoma antigen (TA-4) in penile carcinoma. Urology 36(4):315–317

    Article  PubMed  CAS  Google Scholar 

  40. Laniado ME, Lowdell C, Mitchell H, Christmas TJ (2003) Squamous cell carcinoma antigen: a role in the early identification of nodal metastases in men with squamous cell carcinoma of the penis. BJU Int 92(3):248–250

    Article  PubMed  CAS  Google Scholar 

  41. Touloupidis S, Zisimopoulos A, Giannakopoulos S, Papatsoris AG, Kalaitzis C, Thanos A (2007) Clinical usage of the squamous cell carcinoma antigen in patients with penile cancer. Int J Urol 14(2):174–176

    Article  PubMed  CAS  Google Scholar 

  42. Hungerhuber E, Schlenker B, Schneede P, Stief CG, Karl A (2007) Squamous cell carcinoma antigen correlates with tumor burden but lacks prognostic potential for occult lymph node metastases in penile cancer. Urology 70(5):975–979

    Article  PubMed  Google Scholar 

  43. Medina PM, Valero PJ, Martinez Igarzabal MJ (1999) Verrucous carcinoma of the penis with intense basal expression of Ki 67. Arch Esp Urol 52(9):983–985

    Google Scholar 

  44. Gentile V, Vicini P, Giacomelli L, Cardillo MR, Pierangeli A, Degener AM (2006) Detection of human papillomavirus DNA, p53 and ki67 expression in penile carcinomas. Int J Immunopathol Pharmacol 19(1):209–215

    PubMed  CAS  Google Scholar 

  45. Berdjis N, Meye A, Nippgen J, Dittert D, Hakenberg O, Baretton GB et al (2005) Expression of Ki-67 in squamous cell carcinoma of the penis. BJU Int 96(1):146–148

    Article  PubMed  CAS  Google Scholar 

  46. Guimaraes GC, Leal ML, Campos RS, Zequi SC, da Fonseca FP, da Cunha IW et al (2007) Do proliferating cell nuclear antigen and MIB-1/Ki-67 have prognostic value in penile squamous cell carcinoma? Urology 70(1):137–142

    Article  PubMed  Google Scholar 

  47. Dervan PA, Magee HM, Buckley C, Carney DN (1992) Proliferating cell nuclear antigen counts in formalin-fixed paraffin-embedded tissue correlate with Ki-67 in fresh tissue. Am J Clin Pathol 97(5 Suppl 1):S21–S28

    PubMed  CAS  Google Scholar 

  48. Waseem NH, Lane DP (1990) Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form. J Cell Sci 96(Pt 1):121–129

    PubMed  CAS  Google Scholar 

  49. Martins AC, Faria SM, Velludo MAL (2000) Carcinoma of the penis: value of proliferating cell nuclear antigen (PCNA). Int Braz J Urol 26:38–42

    Google Scholar 

  50. Campos RS, Lopes A, Guimaraes GC, Carvalho AL, Soares FA (2006) E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of 125 patients. Urology 67(4):797–802

    Article  PubMed  Google Scholar 

  51. Kusukawa J, Sasaguri Y, Shima I, Kameyama T, Morimatsu M (1993) Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. A clinicopathologic study. Am J Clin Pathol 99(1):18–23

    PubMed  CAS  Google Scholar 

  52. Vihinen P, Kahari VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99(2):157–166

    Article  PubMed  CAS  Google Scholar 

  53. Couturier J, Sastre-Garau X, Schneider-Maunoury S, Labib A, Orth G (1991) Integration of papillomavirus DNA near myc genes in genital carcinomas and its consequences for proto-oncogene expression. J Virol 65(8):4534–4538

    PubMed  CAS  Google Scholar 

  54. Sastre-Garau X, Favre M, Couturier J, Orth G (2000) Distinct patterns of alteration of myc genes associated with integration of human papillomavirus type 16 or type 45 DNA in two genital tumours. J Gen Virol 81(Pt 8):1983–1993

    PubMed  CAS  Google Scholar 

  55. Leis PF, Stevens KR, Baer SC, Kadmon D, Goldberg LH, Wang XJ (1998) A c-rasHa mutation in the metastasis of a human papillomavirus (HPV)-18 positive penile squamous cell carcinoma suggests a cooperative effect between HPV-18 and c-rasHa activation in malignant progression. Cancer 83(1):122–129

    Article  PubMed  CAS  Google Scholar 

  56. Golijanin D, Tan JY, Kazior A, Cohen EG, Russo P, Dalbagni G et al (2004) Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis. Clin Cancer Res 10(3):1024–1031

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, University College London Hospital, 235 Euston Road, London, UK

    Asif Muneer, O. Kayes, Hashim U. Ahmed, Manit Arya & Suks Minhas

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  1. Asif Muneer
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  2. O. Kayes
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  3. Hashim U. Ahmed
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Correspondence to Asif Muneer.

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Muneer, A., Kayes, O., Ahmed, H.U. et al. Molecular prognostic factors in penile cancer. World J Urol 27, 161–167 (2009). https://doi.org/10.1007/s00345-008-0275-y

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