Immunohistochemical Detection of p16 in Clinical Samples

Abstract

P16 immunohistochemical expression, a surrogate marker of the retinoblastoma pathway, has become a major adjunct in the routine practice mostly of cervical and head/neck pathology, but with other indications too. In this chapter, a detailed immunohistochemical technique for the detection of p16 is described, followed by indications and interpretation of its expression in uterine, ovarian, vulvar, penile, head-and-neck, melanocytic, and other pathologies.

Cytoplasmic p16 Is Expressed in Normal Brown Fat and Hibernomas

“…9 P16 IHC has been extensively used in other pathologies and especially in the routine practice of uterine cervix or head and neck pathology, as its interpretation is important for the management of human papillomavirus–associated lesions. 10-13 During human papillomavirus infection, the E7 viral protein degrades retinoblastoma protein, causing constant activation of the nuclear factor E2F, which then activates its target genes. 10 p16 levels rise, but the normal feedback is bypassed.…”

“…10-13 During human papillomavirus infection, the E7 viral protein degrades retinoblastoma protein, causing constant activation of the nuclear factor E2F, which then activates its target genes. 10 p16 levels rise, but the normal feedback is bypassed. This p16 overexpression has diagnostic utility in these pathologies.…”

“…This p16 overexpression has diagnostic utility in these pathologies. In other forms of cancer, like mesotheliomas or melanomas, there is a genetic inactivation of p16 , and it is this detection that has diagnostic significance, 10,14,15 while in several other tumors, wild-type or mutant p16 overexpression is observed and associated with more aggressive neoplasms, but through unknown mechanisms. 16 p16 overexpression in these cases may be an attempt to restore p16 functions, but its negative impact on cellular proliferation can be avoided or prevented by alternative molecular events.…”

“…2,9 However, in uterine cervix and head and neck pathology, both nuclear and cytoplasmic strong and diffuse expression is the definition criterion for p16 positivity. 10 Thus, what does a cytoplasmic-only expression mean? In lipomatous lesions, no data exist, to the best of our knowledge, that could answer this question.…”