{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T22:38:51Z","timestamp":1778539131709,"version":"3.51.4"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T00:00:00Z","timestamp":1290038400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2011,2]]},"DOI":"10.1007\/s00428-010-1007-4","type":"journal-article","created":{"date-parts":[[2010,11,17]],"date-time":"2010-11-17T13:45:20Z","timestamp":1290001520000},"page":"221-229","source":"Crossref","is-referenced-by-count":86,"title":["Alterations in the tumor suppressor gene p16 INK4A are associated with aggressive behavior of penile carcinomas"],"prefix":"10.1007","volume":"458","author":[{"given":"Micaela","family":"Poetsch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hemmerich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Kakies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britta","family":"Kleist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"vom Dorp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver W.","family":"Hakenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Protzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,11,18]]},"reference":[{"key":"1007_CR1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cell.2006.10.003","volume":"127","author":"WY Kim","year":"2006","unstructured":"Kim WY, Sharpless NE (2006) The regulation of INK4\/ARF in cancer and aging. Cell 127:265\u2013275","journal-title":"Cell"},{"key":"1007_CR2","first-page":"3689","volume":"60","author":"CJ Sherr","year":"2000","unstructured":"Sherr CJ (2000) The Pezcoller lecture: cancer cell cycles revisited. Cancer Res 60:3689\u20133695","journal-title":"Cancer Res"},{"key":"1007_CR3","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.virol.2008.11.046","volume":"384","author":"H zur Hausen","year":"2009","unstructured":"zur Hausen H (2009) Papillomaviruses in the causation of human cancers\u2014a brief historical account. Virology 384:260\u2013265","journal-title":"Virology"},{"key":"1007_CR4","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/ijc.2910520513","volume":"52","author":"N Munoz","year":"1992","unstructured":"Munoz N, Bosch FX, de Sanjose S, Tafur L, Izarzugaza I, Gili M, Viladiu P, Navarro C, Martos C, Ascunce N et al (1992) The causal link between human papillomavirus and invasive cervical cancer: a population-based case\u2013control study in Colombia and Spain. Int J Cancer 52:743\u2013749","journal-title":"Int J Cancer"},{"key":"1007_CR5","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1200\/JCO.2004.00.3335","volume":"24","author":"PM Weinberger","year":"2006","unstructured":"Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, Sasaki C, Joe J, Camp RL, Rimm DL, Psyrri A (2006) Molecular classification identifies a subset of human papillomavirus-associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 24:736\u2013747","journal-title":"J Clin Oncol"},{"key":"1007_CR6","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/S0002-9440(10)62506-0","volume":"159","author":"MA Rubin","year":"2001","unstructured":"Rubin MA, Kleter B, Zhou M, Ayala G, Cubilla AL, Quint WG, Pirog EC (2001) Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol 159:1211\u20131218","journal-title":"Am J Pathol"},{"key":"1007_CR7","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/ijc.21961","volume":"119","author":"AP Lont","year":"2006","unstructured":"Lont AP, Kroon BK, Horenblas S, Gallee MP, Berkhof J, Meijer CJ, Snijders PJ (2006) Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival. Int J Cancer 119:1078\u20131081","journal-title":"Int J Cancer"},{"key":"1007_CR8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1440-1827.2008.02259.x","volume":"58","author":"N Yanagawa","year":"2008","unstructured":"Yanagawa N, Osakabe M, Hayashi M, Tamura G, Motoyama T (2008) Detection of HPV-DNA, p53 alterations, and methylation in penile squamous cell carcinoma in Japanese men. Pathol Int 58:477\u2013482","journal-title":"Pathol Int"},{"key":"1007_CR9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/path.1394","volume":"201","author":"E Ferreux","year":"2003","unstructured":"Ferreux E, Lont AP, Horenblas S, Gallee MPW, Raaphorst FM, von Knebel DM, Meijer CJLM, Snijders PJF (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 201:109\u2013118","journal-title":"J Pathol"},{"key":"1007_CR10","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/modpathol.3800931","volume":"20","author":"M Poetsch","year":"2007","unstructured":"Poetsch M, Schuart B-J, Schwesinger G, Kleist B, Protzel C (2007) Screening of microsatellite markers in penile cancer reveals differences between metastatic and non-metastatic carcinomas. Mod Pathol 20:1069\u20131077","journal-title":"Mod Pathol"},{"key":"1007_CR11","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/sj.bjc.6602928","volume":"94","author":"S Forbes","year":"2006","unstructured":"Forbes S, Clements J, Dawson E, Bamford S, Webb T, Dogan A, Flanagan A, Teague J, Wooster R, Futreal PA, Stratton MR (2006) Cosmic 2005. Br J Cancer 94:318\u2013322","journal-title":"Br J Cancer"},{"key":"1007_CR12","first-page":"3225","volume":"61","author":"M Esteller","year":"2001","unstructured":"Esteller M, Corn PF, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 61:3225\u20133229","journal-title":"Cancer Res"},{"key":"1007_CR13","volume-title":"TNM classification of malignant tumours","author":"LH Sobin","year":"2002","unstructured":"Sobin LH, Wittekind C (2002) TNM classification of malignant tumours, 6th edn. Wiley-Liss, New York","edition":"6"},{"key":"1007_CR14","first-page":"280","volume-title":"World Health Organization classification of tumours. Pathology and genetics of tumours of the urinary system and male genital organs","author":"JN Eble","year":"2004","unstructured":"Eble JN, Sauter G, Epstein JI, Sesterhenn IA (2004) World Health Organization classification of tumours. Pathology and genetics of tumours of the urinary system and male genital organs. IARC, Lyon, pp 280\u2013290"},{"key":"1007_CR15","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00345-006-0109-8","volume":"24","author":"K Hendricksen","year":"2006","unstructured":"Hendricksen K, Moonen PM, der Heijden AG, Witjes JA (2006) False-positive lesions detected by fluorescence cystoscopy: any association with p53 and p16 expression? World J Urol 24:597\u2013601","journal-title":"World J Urol"},{"key":"1007_CR16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/01.pas.0000213347.65014.ee","volume":"31","author":"CS Kong","year":"2007","unstructured":"Kong CS, Balzer BL, Troxell ML, Patterson BK, Longacre TA (2007) p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk HPV in atypical squamous metaplasia. Am J Surg Pathol 31:33\u201343","journal-title":"Am J Surg Pathol"},{"key":"1007_CR17","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1097\/PAS.0b013e3181cfcac7","volume":"34","author":"EB Stelow","year":"2010","unstructured":"Stelow EB, Shaco-Levy R, Bao F, Garcia J, Klimstra DS (2010) Pancreatic acinar cell carcinomas with prominent ductal differentiation: mixed acinar ductal carcinoma and mixed acinar endocrine ductal carcinoma. Am J Surg Pathol 34:510\u2013518","journal-title":"Am J Surg Pathol."},{"key":"1007_CR18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0165-4608(00)00353-8","volume":"125","author":"M Poetsch","year":"2001","unstructured":"Poetsch M, Dittberner T, Woenckhaus C (2001) PTEN\/MMAC1 in malignant melanoma and its importance for tumour progression. Cancer Genet Cytogenet 125:21\u201326","journal-title":"Cancer Genet Cytogenet"},{"key":"1007_CR19","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1593\/neo.05163","volume":"7","author":"M Poetsch","year":"2005","unstructured":"Poetsch M, Zimmermann A, Wolf E, Kleist B (2005) Loss of heterozygosity occurs predominantly, but not exclusively in the epithelial compartment of pleomorphic adenoma. Neoplasia 7:688\u2013695","journal-title":"Neoplasia"},{"key":"1007_CR20","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1128\/JCM.42.7.3176-3184.2004","volume":"42","author":"K Sotlar","year":"2004","unstructured":"Sotlar K, Diemer D, Dethleffs A, Hack Y, Stubner A, Vollmer N, Menton S, Menton M, Dietz K, Wallwiener D, Kandolf R, B\u00fcltmann B (2004) Detection and typing of human papillomavirus by E6 nested multiplex PCR. J Clin Microbiol 42:3176\u20133184","journal-title":"J Clin Microbiol"},{"key":"1007_CR21","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/S0165-4608(01)00509-X","volume":"132","author":"M Poetsch","year":"2002","unstructured":"Poetsch M, Lorenz G, Kleist B (2002) Detection of new PTEN\/MMAC1 mutations in head and neck squamous cell carcinomas with loss of chromosomes 10. Cancer Genet Cytogenet 132:20\u201324","journal-title":"Cancer Genet Cytogenet"},{"key":"1007_CR22","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.ejca.2007.01.032","volume":"43","author":"M Yano","year":"2007","unstructured":"Yano M, Hamatani K, Eguchi H, Hirai Y, MacPhee DG, Sugino K, Dohi K, Itamoto T, Asahara T (2007) Prognosis in patients with hepatocellular carcinoma correlates to mutations of p53 and\/or hMSH2 genes. Eur J Cancer 43:1092\u20131100","journal-title":"Eur J Cancer"},{"key":"1007_CR23","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1593\/neo.05586","volume":"8","author":"Y Liu","year":"2006","unstructured":"Liu Y, Lan Q, Siegfried JM, Luketich JD, Keohavong P (2006) Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients. Neoplasia 8:46\u201351","journal-title":"Neoplasia"},{"key":"1007_CR24","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1365-2133.2007.08305.x","volume":"158","author":"DM Prowse","year":"2008","unstructured":"Prowse DM, Ktori EN, Chandrasekaran D, Prapa A, Baithun S (2008) Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcioma. Br J Dermatol 158:261\u2013265","journal-title":"Br J Dermatol"},{"key":"1007_CR25","first-page":"177","volume":"22","author":"A Pascual","year":"2007","unstructured":"Pascual A, Pariente M, Godinez JM, S\u00e1nchez-Prieto R, Atienzar M, Segura M, Poblet E (2007) High prevalence of human papillomavirus 16 in penile carcinoma. Histol Histopathol 22:177\u2013183","journal-title":"Histol Histopathol"},{"key":"1007_CR26","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/modpathol.2009.77","volume":"22","author":"E Stankiewicz","year":"2009","unstructured":"Stankiewicz E, Kudahette SC, Prowse DM, Ktori E, Cuzick J, Ambroisine L, Zhang X, Watkin N, Corbishley C, Berney DM (2009) HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis. Mod Pathol 22:1160\u20131168","journal-title":"Mod Pathol"},{"key":"1007_CR27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F","volume":"189","author":"JM Walboomers","year":"1999","unstructured":"Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PF, Peto J, Meijer CJ, Munoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12\u201319","journal-title":"J Pathol"},{"key":"1007_CR28","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1002\/cncr.25033","volume":"116","author":"AD Singhi","year":"2010","unstructured":"Singhi AD, Westra WH (2010) Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience. Cancer 116:2166\u20132173","journal-title":"Cancer"},{"key":"1007_CR29","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1158\/1055-9965.EPI-09-0209","volume":"18","author":"HP Nieuwenhof van de","year":"2009","unstructured":"van de Nieuwenhof HP, van Kempen LC, de Hullu JA, Bekkers RL, Bulten J, Melchers WJ, Massuger LF (2009) The etiologic role of HPV in vulvar squamous cell carcinoma fine tuned. Cancer Epidemiol Biomarkers Prev 18:2061\u20132067","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"1007_CR30","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/00313020802035907","volume":"40","author":"NJ Mulvany","year":"2008","unstructured":"Mulvany NJ, Allen DG, Wilson SM (2008) Diagnostic utility of p16INK4a: a reappraisal of its use in cervical biopsies. Pathology 40:335\u2013344","journal-title":"Pathology"},{"key":"1007_CR31","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/j.1365-2559.2006.02340.x","volume":"48","author":"L Galmiche","year":"2006","unstructured":"Galmiche L, Coste-Burel M, Lopez P, Phillippe HJ, Laboisse C (2006) The expression of p16INK4a is not correlated with HPV status in CIN 1. Histopathology 48:767","journal-title":"Histopathology"},{"key":"1007_CR32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4149\/av_2009_01_43","volume":"53","author":"M Senba","year":"2009","unstructured":"Senba M, Buziba N, Mori N, Wada A, Irie S, Toriyama K (2009) Detection of human papillomavirus and cellular regulators p16INK4a, p53, and NF.kappaB in penile cancer cases in Kenya. Acta Virol 53:43\u201348","journal-title":"Acta Virol"},{"key":"1007_CR33","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1750-9378-5-4","volume":"5","author":"EM Smith","year":"2010","unstructured":"Smith EM, Rubenstein LM, Hoffman H, Haugen TH, Turek LP (2010) Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer. Infect Agent Cancer 5:4","journal-title":"Infect Agent Cancer"},{"key":"1007_CR34","doi-asserted-by":"crossref","first-page":"4474","DOI":"10.1002\/cncr.25304","volume":"116","author":"E Karamitopoulou","year":"2010","unstructured":"Karamitopoulou E, Zlober I, Koumarianou A, Patsouris ES, Peros G, Lugli A (2010) Expression of p16 in lymph node metastases of adjuvantly treated stage III colorectal cancer patients identifies poor prognostic subgroups: a retrospective analysis of biomarkers in matched primary tumor and lymph node metastases. Cancer 116:4474\u20134486","journal-title":"Cancer"},{"key":"1007_CR35","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/sj.bjc.6604457","volume":"99","author":"P Schulz","year":"2008","unstructured":"Schulz P, Scholz A, Rexin A, Hauff P, Schirner M, Wiedenmann B, Detjen K (2008) Inducible re-expression of p16 in an orthotopic mouse model of pancreatic cancer inhibits lymphangiogenesis and lymphatic metastasis. Br J Cancer 99:110\u2013117","journal-title":"Br J Cancer"},{"key":"1007_CR36","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0022-5347(05)64836-7","volume":"168","author":"A Lopes","year":"2002","unstructured":"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 168:81\u201386","journal-title":"J Urol"},{"key":"1007_CR37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0022-5347(05)65389-X","volume":"167","author":"AC Martins","year":"2002","unstructured":"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 167:89\u201393","journal-title":"J Urol"},{"key":"1007_CR38","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/(SICI)1097-0215(19980610)76:6<779::AID-IJC1>3.0.CO;2-V","volume":"76","author":"JE Levi","year":"1998","unstructured":"Levi JE, Rahal P, Sarkis AS, Villa L (1998) Human papillomarvirus DNA and p53 status in penile carcinomas. Int J Cancer 76:779\u2013783","journal-title":"Int J Cancer"},{"key":"1007_CR39","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/205873920601900121","volume":"19","author":"V Gentile","year":"2006","unstructured":"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 19:209\u2013215","journal-title":"Int J Immunopathol Pharmacol"},{"key":"1007_CR40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.urolonc.2010.03.021","volume":"28","author":"PJ Goebell","year":"2010","unstructured":"Goebell PJ, Groshen SG, Schmitz-Drager BJ (2010) p53 immunohistochemistry in bladder cancer\u2014a new approach to an old question. Urol Oncol 28:377\u2013388","journal-title":"Urol Oncol"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-010-1007-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00428-010-1007-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-010-1007-4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T08:48:06Z","timestamp":1711961286000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00428-010-1007-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,18]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,2]]}},"alternative-id":["1007"],"URL":"https:\/\/doi.org\/10.1007\/s00428-010-1007-4","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,18]]}}}