Electron microscopy evidence that cytoplasmic localization of the p16(INK4A) "nuclear" cyclin-dependent kinase inhibitor (CKI) in tumor cells is specific and not an artifact. A study in non-small cell lung carcinomas

Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission
K EvangelouV G Gorgoulis

Abstract

It is well established that p16(INK4A) protein acts as a cell cycle inhibitor in the nucleus. Therefore, cytoplasmic localization of p16 (INK4A) usually is disregarded by investigators as nonspecific. Three recent studies reported findings that differ from the current view concerning p16(INK4A) immunohistochemical localization. All three demonstrated that breast and colon cancers expressing cytoplasmic p16(INK4) represent distinct biological subsets. We previously detected in a percentage of non-small cell lung carcinomas simultaneous nuclear and cytoplasmic p16(INK4A) staining. In view of the reports concerning breast and colon carcinomas, we conducted an ultrastructural re-evaluation of our cases to clarify the specificity of p16(INK4A) cytoplasmic expression. We observed p16 (INK4A) immunolocalization in both the nucleus and the cytoplasm of a proportion of tumor cells. Diffuse dense nuclear staining was detected in the nucleoplasm, whereas weaker granular immunoreactivity was observed in the cytoplasm near the rough endoplasmic reticulum. Negative tumor cells also were visible. In the tumor-associated stromal, cells p16(INK4A) immunoreactivity was detected only in the nuclei. We have demonstrated that p16(INK4A) cytoplasmic...Continue Reading

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Citations

Nov 4, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bonnie E Gould RothbergDavid L Rimm
Nov 30, 2012·The Journal of Investigative Dermatology·Noah C JenkinsDouglas Grossman
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Feb 5, 2009·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Waranun BuajeebSirima Sanguansin
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