Top

World Journal of Urology

Published in:

01-04-2009 | Topic Paper

Molecular prognostic factors in penile cancer

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

Published in: World Journal of Urology | Issue 2/2009

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.

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

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

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):1105–1112PubMedCrossRef

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):705–711PubMedCrossRef

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):1637–1642PubMedCrossRef

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):1700–1704PubMedCrossRef

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):1211–1218PubMed

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):606–616PubMedCrossRef

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):65–69PubMedCrossRef

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):1341–1346PubMedCrossRef

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):35–44PubMedCrossRef

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):1247–1255PubMedCrossRef

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):4550–4556PubMedCrossRef

14.

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

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):1–6PubMedCrossRef

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):2315–2321PubMedCrossRef

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):694–701PubMedCrossRef

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):1078–1081PubMedCrossRef

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):77–79PubMedCrossRef

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):78–79PubMedCrossRef

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):48–53PubMedCrossRef

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):111–116PubMedCrossRef

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):48–55PubMed

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):72–77PubMed

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):67–70PubMed

26.

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

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):81–86PubMedCrossRef

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):895–904PubMed

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):684–690PubMedCrossRef

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):248–256PubMed

31.

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

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):4059–4070PubMedCrossRef

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):89–92PubMedCrossRef

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):204–208PubMedCrossRef

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):261–265PubMedCrossRef

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):109–118PubMedCrossRef

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):433–439PubMed

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):730–734PubMedCrossRef

39.

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

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):248–250PubMedCrossRef

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):174–176PubMedCrossRef

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):975–979PubMedCrossRef

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

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):209–215PubMed

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):146–148PubMedCrossRef

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):137–142PubMedCrossRef

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–S28PubMed

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):121–129PubMed

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

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):797–802PubMedCrossRef

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):18–23PubMed

52.

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

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):4534–4538PubMed

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):1983–1993PubMed

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):122–129PubMedCrossRef

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):1024–1031PubMedCrossRef

Title: Molecular prognostic factors in penile cancer
Authors: Asif Muneer
O. Kayes
Hashim U. Ahmed
Manit Arya
Suks Minhas
Publication date: 01-04-2009
Publisher: Springer-Verlag
Published in: World Journal of Urology / Issue 2/2009
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-008-0275-y

At a glance: The STEP trials

Springer Medicine

Molecular prognostic factors in penile cancer

Abstract

Objectives

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2009

Pure laparoscopic complete excision of distal ureter with a bladder cuff for upper tract urothelial carcinoma

Non-invasive and minimally invasive staging of regional lymph nodes in penile cancer

17β-Estradiol affects the proliferation and apoptosis of rat bladder neck smooth muscle cells by modulating cell cycle transition and related proteins

Collecting system involvement by renal tumor: are CT measurements reliable enough?

Penile cancer: epidemiology, pathogenesis and prevention

Prediction of Gleason score upgrading in low-risk prostate cancers diagnosed via multi (≥12)-core prostate biopsy