Distinctive association of p16INK4a overexpression with penile intraepithelial neoplasia depicting warty and/or basaloid features: A study of 141 cases evaluating a new nomenclature

American Journal of Surgical Pathology

Volumn 34, Issue 3, 2010, Pages 385-392

  Chaux, Alcides ^a   Pfannl, Rolf ^b   Lloveras, Belén ^e,f   Alejo, María ^f,g   Clavero, Omar ^f   Lezcano, Cecilia ^a   Muñoz, Nubia ^f   De Sanjosé, Silvia ^f,h   Bosch, Xavier ^f   Hernández Pérez, Marier ^c   Velazquez, Elsa F ^d   Cubilla, Antonio L ^a  

^a INSTITUTO DE PATOLOGÍA E INVESTIGACIÓN   (Paraguay)

^b TUFTS MEDICAL CENTER   (United States)

^c BOSTON MEDICAL CENTER   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e IMAS IMIN   (Spain)

^f CATALAN INSTITUTE OF ONCOLOGY   (Spain)

^g Hospital General de LHospitalet   (Spain)

^h CIBER EPIDEMIOLOGÍA Y SALUD PÚBLICA CIBERESP   (Spain)

Author keywords

HPV; Penile cancer; Penile intraepithelial neoplasia

Indexed keywords

EID: 77649224088     PISSN: 01475185     EISSN: 15320979     Source Type: Journal    
DOI: 10.1097/PAS.0b013e3181cdad23     Document Type: Article

References (58)

1. Agoff SN, Lin P, Morihara J, et al. p16(INK4a) expression correlates with degree of cervical neoplasia: a comparison with Ki-67 expression and detection of high-risk HPV types. Mod Pathol. 2003;16:665-673.
2. Ansari-Lari MA, Staebler A, Zaino RJ, et al. Distinction of endocervical and endometrial adenocarcinomas: immunohisto-chemical p16 expression correlated with human papillomavirus (HPV) DNA detection. Am J Surg Pathol. 2004;28:160-167.
3. Bean SM, Eltoum I, Horton DK, et al. Immunohistochemical expression of p16 and Ki-67 correlates with degree of anal intraepithelial neoplasia. Am J Surg Pathol. 2007;31:555-561.
4. Benevolo M, Mottolese M, Marandino F, et al. Immunohistochemical expression of p16(INK4a) is predictive of HR-HPV infection in cervical low-grade lesions. Mod Pathol. 2006;19:384-391.
5. Chan MK, Cheung TH, Chung TK, et al. Expression of p16INK4 and retinoblastoma protein Rb in vulvar lesions of Chinese women. Gynecol Oncol. 1998;68:156-161.
6. Collinson P. Of bombers, radiologists, and cardiologists: time to ROC. Heart. 1998;80:215-217.
7. Cubilla AL. The role of pathologic prognostic factors in squamous cell carcinoma of the penis. World J Urol. 2009;27:169-177.
8. Cubilla AL, Meijer CJ, Young RH. Morphological features of epithelial abnormalities and precancerous lesions of the penis. Scand J. Urol Nephrol Suppl. 2000;Suppl 205:215-219.
9. Cubilla AL, Alejo M, Lloveras B, et al. The value of p16NK4a as a histomarker for HPV in subtypes of penile squamous cell carcinoma (SCC): A study of 158 tumors. Mod Pathol. 2009;22:164A.
10. Cubilla AL, Lloveras B, Alejo M, et al. The basaloid cell is the best tissue marker for human papillomavirus (HPV) in invasive penile squamous cell carcinoma: a study of 202 cases. Am J Surg Pathol. 2009. In press.
11. Cunningham LL Jr, Pagano GM, Li M, et al. Overexpression of p16INK4 is a reliable marker of human papillomavirus-induced oral high-grade squamous dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:77-81.
12. Dehn D, Torkko KC, Shroyer KR. Human papillomavirus testing and molecular markers of cervical dysplasia and carcinoma. Cancer. 2007;111:1-14.
13. Epstein JH, Humphrey PA, Cubilla AL. Tumors of the Prostate Gland, Seminal Vesicles, Male Urethra, Penis and Scrotum. Washington, D.C.: Armed Forces Institute of Pathology; 2009.
14. Fawcett T. An introduction to ROC analysis. Pattern Recog Lett. 2006;27:861-874.
15. Finegan MM, Han AC, Edelson MI, et al. p16 expression in squamous lesions of the female genital tract. J Mol Histol. 2004; 35:111-114.
16. Godoy AE, Mandelli J, Oliveira FH, et al. p16INK4 expression in precursor lesions of squamous cell cervical cancer related to the presence of HPV-DNA. Braz J Med Biol Res. 2008;41:583-588.
17. Gregoire L, Cubilla AL, Reuter VE, et al. Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma. J Natl Cancer Inst. 1995; 87:1705-1709.
18. Hafkamp HC, Speel EJ, Haesevoets A, et al. A subset of head and neck squamous cell carcinomas exhibits integration of HPV 16/18 DNA and overexpression of p16INK4A and p53 in the absence of mutations in p53 exons 5 to 8. Int J Cancer. 2003;107:394-400.
19. Haidopoulos D, Partsinevelos GA, Vlachos GD, et al. p16 INK4A is a strong biomarker for cervical intraepithelial neoplasia and invasive cervical carcinoma: a reappraisal. Reprod Sci. 2009;16:685-693.
20. Hoevenaars BM, Van der Avoort IA, De Wilde PC, et al. A panel of p16(INK4A), MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma. Int J Cancer. 2008;123:2767-2773.
21. Horn LC, Lindner K, Szepankiewicz G, et al. p16, p14, p53, and cyclin D1 expression and HPV analysis in small cell carcinomas of the uterine cervix. Int J Gynecol Pathol. 2006;25:182-186.
22. Kalof AN, Cooper K. p16INK4a immunoexpression: surrogate marker of high-risk HPV and high-grade cervical intraepithelial neoplasia. Adv Anat Pathol. 2006;13:190-194.
23. Keating JT, Cviko A, Riethdorf S, et al. Ki-67, cyclin E, and p16INK4 are complimentary surrogate biomarkers for human papilloma virus-related cervical neoplasia. Am J Surg Pathol. 2001; 25:884-891.
24. Keating JT, Ince T, Crum CP. Surrogate biomarkers of HPV infection in cervical neoplasia screening and diagnosis. Adv Anat Pathol. 2001;8:83-92.
25. Klussmann JP, Gultekin E, Weissenborn SJ, et al. Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus. Am J Pathol. 2003;162:747-753.
26. Kong CS, Balzer BL, Troxell ML, et al. p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk HPV in atypical squamous metaplasia. Am J Surg Pathol. 2007;31:33-43.
27. Krustrup D, Jensen HL, Van den Brule AJ, et al. Histological characteristics of human papilloma-virus-positive and -negative invasive and in situ squamous cell tumours of the penis. Int J Exp Pathol. 2009;90:182-189.
28. Laco J, Slaninka I, Jirasek M, et al. High-risk human papilloma-virus infection and p16INK4a protein expression in laryngeal lesions. Pathol Res Pract. 2008;204:545-552.
29. Logani S, Lu D, Quint WG, et al. Low-grade vulvar and vaginal intraepithelial neoplasia: correlation of histologic features with human papillomavirus DNA detection and MIB-1 immunostaining. Mod Pathol. 2003;16:735-741.
30. Lu DW, El-Mofty SK, Wang HL. Expression of p16, Rb, and p53 proteins in squamous cell carcinomas of the anorectal region harboring human papillomavirus DNA. Mod Pathol. 2003;16:692-699.
31. Mellin DH, Lindquist D, Bjornestal L, et al. P16(INK4a) correlates to human papillomavirus presence, response to radiotherapy and clinical outcome in tonsillar carcinoma. Anticancer Res. 2005;25:4375-4383.
32. Mulvany NJ, Allen DG, Wilson SM. Diagnostic utility of p16INK4a: a reappraisal of its use in cervical biopsies. Pathology. 2008;40:335-344.
33. Munoz N, Bosch FX, De Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003;348:518-527.
34. Nasca M, Innocenzi D, Micali G. Association of penile lichen sclerosus and oncogenic human papillomavirus infection. Int J Dermatol. 2006;45:681-683.
35. Nasca MR, Innocenzi D, Micali G. Penile cancer among patients with genital lichen sclerosus. J Am Acad Dermatol. 1999;41:911-914.
36. Nieh S, Chen SF, Chu TY, et al. Is p16(INK4A) expression more useful than human papillomavirus test to determine the outcome of atypical squamous cells of undetermined significance-categorized Pap smear? A comparative analysis using abnormal cervical smears with follow-up biopsies. Gynecol Oncol. 2005;97:35-40.
37. Nogueira MC, Guedes NEP, Rosa MW, et al. Immunohistochemical expression of p16 and p53 in vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva. Pathol Oncol Res. 2006; 12:153-157.
38. O'Neill CJ, McCluggage WG. p16 expression in the female genital tract and its value in diagnosis. Adv Anat Pathol. 2006;13:8-15.
39. Ordi J, Alejo M, Fuste V, et al. HPV-negative vulvar intraepithelial neoplasia (VIN) with basaloid histologic pattern: an unrecognized variant of simplex (differentiated) VIN. Am J Surg Pathol. 2009; 33:1659-1665.
40. Ozgul N, Cil AP, Bozdayi G, et al. Staining characteristics of p16INK4a: is there a correlation with lesion grade or high-risk human papilloma virus positivity? J Obstet Gynaecol Res. 2008;34:865-871.
41. Pientong C, Ekalaksananan T, Kongyingyoes B, et al. Immunocytochemical staining of p16INK4a protein from conventional Pap test and its association with human papillomavirus infection. Diagn Cytopathol. 2004;31:235-242.
42. Riethdorf S, Neffen EF, Cviko A, et al. p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias. Hum Pathol. 2004;35:1477-1483.
43. Rubin MA, Kleter B, Zhou M, et al. Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol. 2001;159:1211-1218.
44. Rufforny I, Wilkinson EJ, Liu C, et al. Human papillomavirus infection and p16(INK4a) protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma. J Low Genit Tract Dis. 2005;9:108-113.
45. Ruhul QM, Xu C, Steinhoff MM, et al. Simplex (differentiated) type VIN: absence of p16INK4 supports its weak association with HPV and its probable precursor role in non-HPV related vulvar squamous cancers. Histopathology. 2005;46:718-720.
46. Samama B, Lipsker D, Boehm N. p16 expression in relation to human papillomavirus in anogenital lesions. Hum Pathol. 2006;37:513-519.
47. Santos M, Montagut C, Mellado B, et al. Immunohistochemical staining for p16 and p53 in premalignant and malignant epithelial lesions of the vulva. Int J Gynecol Pathol. 2004;23:206-214.
48. Santos M, Landolfi S, Olivella A, et al. p16 overexpression identifies HPV-positive vulvar squamous cell carcinomas. Am J Surg Pathol. 2006;30:1347-1356.
49. Scurry J, Wilkinson EJ. Review of terminology of precursors of vulvar squamous cell carcinoma. J Low Genit Tract Dis. 2006;10: 161-169.
50. Sideri M, Jones RW, Wilkinson EJ, et al. Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee. J Reprod Med. 2005;50:807-810.
51. Stankiewicz E, Kudahetti SC, Prowse DM, et al. HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis. Mod Pathol. 2009;22:1160-1168.
52. Tsoumpou I, Arbyn M, Kyrgiou M, et al. p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev. 2009;35:210-220.
53. Van der Avoort IA, Shirango H, Hoevenaars BM, et al. Vulvar squamous cell carcinoma is a multifactorial disease following two separate and independent pathways. Int J Gynecol Pathol. 2006; 25:22-29.
54. Velazquez EF, Cubilla AL. Lichen sclerosus in 68 patients with squamous cell carcinoma of the penis: frequent atypias and correlation with special carcinoma variants suggests a precancerous role. Am J Surg Pathol. 2003;27:1448-1453.
55. Wang HL, Lu DW. Detection of human papillomavirus DNA and expression of p16, Rb, and p53 proteins in small cell carcinomas of the uterine cervix. Am J Surg Pathol. 2004;28:901-908.
56. Wang JL, Zheng BY, Li XD, et al. p16INK4A and p14ARF expression pattern by immunohistochemistry in human papilloma-virus-related cervical neoplasia. Mod Pathol. 2005;18:629-637.
57. Willman JH, Heinz D, Golitz LE, et al. Correlation of p16 and pRb expression with HPV detection in Bowen's disease. J Cutan Pathol. 2006;33:629-633.
58. Wittekindt C, Gultekin E, Weissenborn SJ, et al. Expression of p16 protein is associated with human papillomavirus status in tonsillar carcinomas and has implications on survival. Adv Otorhinolaryngol. 2005;62:72-80.