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Updated: Jan 9, 2026

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH
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Published on: August 19, 2014

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Abnormal nuclear and nucleolar immunoreactivity of p16INK4a represents a frameshift alteration in CDKN2A: the E6H4

Ayaka Mitsui1, Jumpei Kashima1,2, Eijitu Ryo2

  • 1Department of Diagnostic Pathology, National Cancer Center Hospital, Japan 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.

Virchows Archiv : an International Journal of Pathology
|December 3, 2025
PubMed

Insights

A distinct p16INK4a staining pattern can mimic HPV-associated cancers. Recognizing this pattern is crucial to prevent misdiagnosis and ensure appropriate patient treatment, especially when using the E6H4 antibody.

Area of Science:

  • Oncology
  • Molecular Pathology
  • Cancer Diagnostics

Background:

  • p16INK4a immunostaining is a key biomarker for human papillomavirus (HPV)-associated cancers.
  • The anti-p16INK4a clone E6H4 is an approved in vitro diagnostic tool for detecting HPV-associated malignancies.

Purpose of the Study:

  • To identify and characterize a distinctive p16INK4a immunostaining pattern.
  • To differentiate this pattern from the established marker for HPV-associated cancers.
  • To elucidate the molecular basis of this aberrant staining pattern.

Main Methods:

  • Immunohistochemistry using the anti-p16INK4a clone E6H4.
  • Analysis of immunostaining patterns in cancer tissues.
  • Investigation of genetic alterations within the INK4a/ARF locus.

Main Results:

  • A unique strong nuclear with nucleolar staining pattern was observed with clone E6H4.
  • This pattern can be mistaken for the typical HPV-associated p16INK4a staining.
  • Frameshift mutations (deletions/insertions) in exon 2 of the INK4a/ARF locus were identified as the cause.

Conclusions:

  • Aberrant p16INK4a immunostaining due to frameshift mutations can mimic HPV-associated cancer markers.
  • Understanding this specific staining pattern is vital for accurate HPV status determination.
  • Avoiding misdiagnosis prevents inappropriate treatment strategies for patients.
Keywords:
CDKN2AFrameshift mutationImmunohistochemistryP14ARFP16INK4a

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