Distinctive Association of p16INK4a Overexpression With Penile Intraepithelial Neoplasia Depicting Warty and/or Basaloid Features: A Study of 141 Cases Evaluating a New Nomenclature
- 1 March 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in The American Journal of Surgical Pathology
- Vol. 34 (3), 385-392
- https://doi.org/10.1097/pas.0b013e3181cdad23
Abstract
From the pathogenic point of view, penile cancers may be grouped in human papillomavirus-related and unrelated tumors, each one of them with distinctive morphologic features. The former are predominantly composed of small, undifferentiated basaloid cells, with more or less prominent koilocytic changes, and the latter of keratinizing differentiated squamous cells. The same cellular types are observed in precancerous lesions. On the basis of these observations, we constructed a novel nomenclature for penile precancerous lesions and classified them as penile intraepithelial neoplasia (PeIN) of differentiated, warty, basaloid, and warty-basaloid types. The aim of this study was to test the usefulness of immunohistochemical p16INK4a overexpression, considered as a surrogate for high-risk human papillomavirus infection, using this classification system. We pathologically evaluated 141 patients with PeIN, associated (123 cases) and unassociated (18 cases) with invasive cancer. Distribution of PeIN types was: differentiated, 72%; basaloid, 9%; warty-basaloid, 7%; warty, 4%; and mixed, 7%. There was a striking similarity in the morphology of in situ and invasive squamous cell carcinomas. Differentiated PeIN was commonly associated with usual, verrucous, papillary, and other low-grade keratinizing variants of squamous cell carcinoma whereas in basaloid and warty carcinomas the presence of in situ lesions with similar morphology was habitual. We evaluated p16INK4a overexpression using a 4-tiered (0, 1, 2, and 3) pattern-based system. To properly distinguish differentiated PeIN from in situ lesions with warty and/or basaloid features only pattern 3, which requires full-thickness staining in all epithelial cells, was considered positive. Using this approach, there was a significant association of the negative patterns and differentiated PeIN and of the positive pattern and warty, basaloid, and warty-basaloid PeIN (PKeywords
This publication has 51 references indexed in Scilit:
- The role of pathologic prognostic factors in squamous cell carcinoma of the penisWorld Journal of Urology, 2008
- Immunohistochemical Expression of p16 and Ki-67 Correlates With Degree of Anal Intraepithelial NeoplasiaThe American Journal of Surgical Pathology, 2007
- Human papillomavirus testing and molecular markers of cervical dysplasia and carcinomaCancer, 2007
- Overexpression of p16INK4 is a reliable marker of human papillomavirus–induced oral high-grade squamous dysplasiaOral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2006
- Immunohistochemical expression of p16INK4a is predictive of HR-HPV infection in cervical low-grade lesionsLaboratory Investigation, 2006
- An introduction to ROC analysisPattern Recognition Letters, 2005
- Distinction of Endocervical and Endometrial AdenocarcinomasThe American Journal of Surgical Pathology, 2004
- p16INK4a Expression Correlates with Degree of Cervical Neoplasia: A Comparison with Ki-67 Expression and Detection of High-Risk HPV TypesLaboratory Investigation, 2003
- Of bombers, radiologists, and cardiologists: time to ROCHeart, 1998
- Expression ofp16INK4and Retinoblastoma ProteinRbin Vulvar Lesions of Chinese WomenGynecologic Oncology, 1998