Stains
p16 INK4a

Author: Nat Pernick, M.D. (see Authors page)

Revised: 2 December 2015, last major update June 2005

Copyright: (c) 2002-2015, PathologyOutlines.com, Inc.

PubMed Search: p16 [title]

Definition / General
  • Also called MTS1, CDKN2A
  • At 9p21 near p15INK4b
  • Plays crucial role in regulation of G1-S transition
  • Tumor suppressor gene that inhibits cyclin D dependent protein kinases CDK4 and CDK6 that prevents phosphorylation of Rb, which prevents its dissociation from E2F transcription factor
    • Prevents cell progression into S phase of cell cycle
  • Frequently silenced in tumors by epigenetic or genetic abnormalities, including promoter CpG methylation or less often mutations

  • Cervix: overexpressed in squamous intraepithelial lesions, particularly HG SIL (97% of biopsies, Mod Pathol 2005;18:267)
  • ALL (pediatric): homozygous deletions noted in 80% of cases with 9p21 abnormalities
  • T-ALL: deleted in 80% of all cases (even with normal #9)
  • Esophageal carcinoma: high frequency of abnormalities
  • Lymphoma: p16 gene methylation present in 60% of pulmonary MALT lymphomas; may be early event (Mod Pathol 2005;18:1187); methylation also associated with Hodgkin’s lymphoma, plaque phase of mycosis fungoides, monoclonal gammopathy of unknown significance
  • Melanoma: abnormalities in 50% of sporadic cases
  • Pancreatic carcinoma: high frequency of abnormalities
  • Squamous cell carcinoma, cutaneous: mutations present
Micro Images
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Full thickness expression

Molecular / Cytogenetics Description
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Full thickness expression