Phosphohistone H3 and Ki-67 labeling indices in cytologic specimens from well-differentiated neuroendocrine tumors of the gastrointestinal tract and pancreas: A comparative analysis using automated image cytometry

Adele D. Fung, Cynthia Cohen, Sravan Kumar Kavuri, Diane Lawson, Xin Gao, Michelle D. Reid

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Ki-67 proliferation index was recently incorporated in the grading of neuroendocrine neoplasms (NENs) of the gastrointestinal tract (GIT) and pancreas. These are now divided into well-differentiated neuroendocrine tumors (WDNETs, grades 1 and 2) and poorly differentiated neuroendocrine carcinomas (grade 3). While Ki-67 is an established proliferation marker in NENs, phosphohistone H3 (PHH3), a newer marker of mitotic activity, is not. Methods: We determined Ki-67 and PHH3 indices on cytologic samples from WDNETs of the GIT and pancreas using an automated cellular imaging system (ACIS®). Results: There was a strong correlation between Ki-67 and PHH3 indices generated by ACIS on cytologic samples. However, in some cases the two stains caused conflicting grades within the same tumor. Conclusion: Both antibodies stain cells in different phases of the cell cycle which may cause discordant grades, thus affecting patient management and prognostication. Ki-67 staining is stronger than PHH3, making 'hot spots' easier to identify on ACIS. Ki-67 is more ideal than PHH3 for staining NENs, especially in tumors with borderline grades. Because PHH3 generates lower mitotic indices it should not be used as a proliferation marker in NENs until its expression has been further characterized.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalActa Cytologica
Volume57
Issue number5
DOIs
StatePublished - Jan 1 2013

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Image Cytometry
Neuroendocrine Tumors
Gastrointestinal Tract
Pancreas
Neoplasms
Coloring Agents
Staining and Labeling
Neuroendocrine Carcinoma
Mitotic Index
Neoplasm Grading
Pancreatic Neoplasms
Cell Cycle
Antibodies

Keywords

  • Automated cellular imaging system
  • Gastrointestinal tract
  • Ki-67 labeling index
  • Pancreas
  • Phosphohistone H3
  • Well-differentiated neuroendocrine tumors

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Phosphohistone H3 and Ki-67 labeling indices in cytologic specimens from well-differentiated neuroendocrine tumors of the gastrointestinal tract and pancreas : A comparative analysis using automated image cytometry. / Fung, Adele D.; Cohen, Cynthia; Kavuri, Sravan Kumar; Lawson, Diane; Gao, Xin; Reid, Michelle D.

In: Acta Cytologica, Vol. 57, No. 5, 01.01.2013, p. 501-508.

Research output: Contribution to journalArticle

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abstract = "Background: Ki-67 proliferation index was recently incorporated in the grading of neuroendocrine neoplasms (NENs) of the gastrointestinal tract (GIT) and pancreas. These are now divided into well-differentiated neuroendocrine tumors (WDNETs, grades 1 and 2) and poorly differentiated neuroendocrine carcinomas (grade 3). While Ki-67 is an established proliferation marker in NENs, phosphohistone H3 (PHH3), a newer marker of mitotic activity, is not. Methods: We determined Ki-67 and PHH3 indices on cytologic samples from WDNETs of the GIT and pancreas using an automated cellular imaging system (ACIS{\circledR}). Results: There was a strong correlation between Ki-67 and PHH3 indices generated by ACIS on cytologic samples. However, in some cases the two stains caused conflicting grades within the same tumor. Conclusion: Both antibodies stain cells in different phases of the cell cycle which may cause discordant grades, thus affecting patient management and prognostication. Ki-67 staining is stronger than PHH3, making 'hot spots' easier to identify on ACIS. Ki-67 is more ideal than PHH3 for staining NENs, especially in tumors with borderline grades. Because PHH3 generates lower mitotic indices it should not be used as a proliferation marker in NENs until its expression has been further characterized.",
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