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No AccessJournal of UrologyAdult Urology1 Mar 2012p16INK4a is a Marker of Good Prognosis for Primary Invasive Penile Squamous Cell Carcinoma: A Multi-Institutional Study Sven Gunia, Andreas Erbersdobler, Oliver W. Hakenberg, Stefan Koch, and Matthias May Sven GuniaSven Gunia Institute of Pathology, HELIOS Clinic Bad Saarow, Bad Saarow, Germany , Andreas ErbersdoblerAndreas Erbersdobler Institute of Pathology, University of Rostock, Rostock, Germany Department of Urology, University of Rostock, Rostock, Germany , Oliver W. HakenbergOliver W. Hakenberg Department of Urology, University of Rostock, Rostock, Germany , Stefan KochStefan Koch Institute of Pathology, HELIOS Clinic Bad Saarow, Bad Saarow, Germany , and Matthias MayMatthias May Department of Urology, St. Elisabeth Clinic Straubing, Straubing, Germany View All Author Informationhttps://doi.org/10.1016/j.juro.2011.10.149AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We assessed the prognostic role of p16INK4a expression in penile cancer with respect to cancer specific survival. Materials and Methods: Based on a multi-institutional collaboration wax embedded tissues from 92 surgically treated patients, including 27 with total and 65 with partial penectomy, were retrospectively evaluated. After a central histopathological review by 1 pathologist a tissue microarray was constructed for p16INK4a immunostaining. Two independent pathologists evaluated p16INK4a expression, which was correlated with cancer specific survival. The κ statistic was used to assess interobserver variability. Univariate and multivariate Cox proportional hazards analysis was applied to assess the independent effects of prognostic factors on cancer specific survival during a median postoperative followup of 32 months (IQR 6–66). Results: The κ statistic revealed excellent interobserver agreement (κ 0.934, p <0.001). Two and 5-year cancer specific survival rates for the entire study cohort were 86% and 74%, respectively. The 2 and 5-year rates for patients without and with p16INK4a expression differed significantly (73% and 57% vs 95% and 85%, respectively, p = 0.011). Univariate analysis revealed p16INK4a expression as a significant prognostic factor with respect to cancer specific survival (p = 0.018). Multivariate analysis identified koilocytosis (HR 0.24, 95% CI 0.07–0.83, p = 0.024), p16INK4a expression (HR 0.44, 95% CI 0.23–0.84, p = 0.013), and histological stage (HR 3.54, 95% CI 1.88–6.67, p <0.001) and grade (HR 2.47, 95% CI 1.00–6.09, p = 0.049) as independent prognostic factors for cancer specific survival. Conclusions: Results show that p16INK4a seems to be a prognostic parameter for primary invasive penile cancer with excellent interobserver reproducibility. At pathology laboratories without antibodies against p16INK4a conventional histological determination of koilocytosis by the pathologist also appears to provide important prognostic information for cancer specific survival. References 1 : How accurate are present risk group assignment tools in penile cancer?. World J Urol2009; 27: 155. Google Scholar 2 : Nomogram predictive of cancer specific survival in patients undergoing partial or total amputation for squamous cell carcinoma of the penis. J Urol2006; 175: 2103. Link, Google Scholar 3 : A simple and accurate model for prediction of cancer-specific mortality in patients treated with surgery for primary penile squamous cell carcinoma. Clin Cancer Res2009; 15: 1013. Google Scholar 4 : Conditional survival predictions after surgery for patients with penile carcinoma. Cancer2011; 117: 3712. Google Scholar 5 : Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med2010; 363: 24. Google Scholar 6 : Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst2008; 100: 261. Google Scholar 7 : Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival. Int J Cancer2006; 119: 1078. Google Scholar 8 : Prognostic significance of human papillomavirus in oropharyngeal squamous cell carcinomas. Laryngoscope2009; 119: 1542. Google Scholar 9 : Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer2001; 91: 2315. Google Scholar 10 : Value of p16INK4a in the pathology of invasive penile squamous cell carcinomas: a report of 202 cases. Am J Surg Pathol2011; 35: 253. Google Scholar 11 : Anatomic levels: important landmarks in penectomy specimens. Am J Surg Pathol2001; 25: 1091. Google Scholar 12 : TNM Classification of Malignant Tumors. In: . Hoboken: Wiley-Blackwell2010: 225. Google Scholar 13 : Squamous-cell epithelioma of the skin: a study of 256 cases. Ann Surg1921; 73: 141. Google Scholar 14 : Comparison of morphologic features and outcome of resected recurrent and nonrecurrent squamous cell carcinoma of the penis: a study of 81 cases. Am J Surg Pathol2009; 33: 1299. Google Scholar 15 : Pathologic features of epidermoid carcinoma of the penis. Am J Surg Pathol1993; 17: 753. Google Scholar 16 : Recommendations for the reporting of surgically resected specimens of colorectal carcinoma: Association of Directors of Anatomic and Surgical Pathology. Am J Clin Pathol2008; 29: 13. Google Scholar 17 : Warty (condylomatous) squamous cell carcinoma of the penis: a report of 11 cases and proposed classification of "verruciform" penile tumors. Am J Surg Pathol2000; 24: 505. Google Scholar 18 : Tumor-associated tissue eosinophilia of penile cancer. Int J Urol2002; 9: 82. Google Scholar 19 : Tissue microarray (TMA) technology: miniaturized pathology archives for high-throughput in situ studies. J Pathol2001; 195: 72. Google Scholar 20 : Distinctive association of p16INK4a overexpression with penile intraepithelial neoplasia depicting warty and/or basaloid features: a study of 141 cases evaluating a new nomenclature. Am J Surg Pathol2010; 34: 385. Google Scholar 21 : EAU penile cancer guidelines 2009. Eur Urol2010; 57: 1002. Google Scholar 22 : Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis. J Urol2006; 175: 1700. Link, Google Scholar 23 : Lymph node metastasis in intermediate-risk penile squamous cell cancer: a two-centre experience. Eur Urol2010; 57: 688. Google Scholar 24 : Nodal staging in penile carcinoma by dynamic sentinel node biopsy after previous therapeutic primary tumour resection. Eur Urol2010; 58: 748. Google Scholar 25 : Prognostic factors for occult inguinal lymph node involvement in penile carcinoma and assessment of the high-risk EAU subgroup: a two-institution analysis of clinically node-negative patients. Eur Urol2010; 58: 742. Google Scholar 26 : Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients. Eur Urol2008; 54: 161. Google Scholar 27 : Molecular prognostic factors in penile cancer. World J Urol2009; 27: 161. Google Scholar 28 : Active transcriptional repression by the Rb-E2F complex mediates G1 arrest triggered by p16INK4a, TGFbeta, and contact inhibition. Cell1999; 97: 53. Google Scholar 29 : Alterations in the tumor suppressor gene p16INK4a are associated with aggressive behavior of penile carcinomas. Virchows Arch2011; 458: 221. Google Scholar 30 : Prognostic factors in invasive squamous cell carcinoma of the penis: analysis of 196 patients treated at the Brazilian National Cancer Institute. J Urol2008; 180: 1354. Link, Google Scholar © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byHartz J, Engelmann D, Fürst K, Marquardt S, Spitschak A, Goody D, Protzel C, Hakenberg O and Pützer B (2016) Integrated Loss of miR-1/miR-101/miR-204 Discriminates Metastatic from Nonmetastatic Penile Carcinomas and Can Predict Patient OutcomeJournal of Urology, VOL. 196, NO. 2, (570-578), Online publication date: 1-Aug-2016.Tang D, Clark P, Giannico G, Hameed O, Chang S and Gellert L (2014) Lack of P16ink4a Over Expression in Penile Squamous Cell Carcinoma is Associated with Recurrence after Lymph Node DissectionJournal of Urology, VOL. 193, NO. 2, (519-525), Online publication date: 1-Feb-2015. Volume 187Issue 3March 2012Page: 899-907 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Keywordscyclin-dependent kinase inhibitor p16penismortalitycarcinomaprognosissquamous cellAcknowledgmentsDrs. V. Henn, Department of Pathology, Ruppiner Clinics, Neuruppin; J. Jander, Department of Pathology, Rhön Clinic Frankfurt/Oder, Frankfurt/Oder; H. Lobeck, Department of Pathology, Ernst-von-Bergmann Clinic Potsdam, Potsdam; and R. Pauli, Department of Pathology, Health Care Centre Brandenburg an der Havel, Brandenburg an der Havel; and M. Tuffaha, Carl-Thiem Clinic Cottbus, Cottbus, Germany, provided archival wax embedded tissue.MetricsAuthor Information Sven Gunia Institute of Pathology, HELIOS Clinic Bad Saarow, Bad Saarow, Germany More articles by this author Andreas Erbersdobler Institute of Pathology, University of Rostock, Rostock, Germany Department of Urology, University of Rostock, Rostock, Germany More articles by this author Oliver W. Hakenberg Department of Urology, University of Rostock, Rostock, Germany More articles by this author Stefan Koch Institute of Pathology, HELIOS Clinic Bad Saarow, Bad Saarow, Germany More articles by this author Matthias May Department of Urology, St. Elisabeth Clinic Straubing, Straubing, Germany More articles by this author Expand All Advertisement PDF downloadLoading ...
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