Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

Mahmoud Goodarzi, Arlene M. Correa, Jaffer A. Ajani, Stephen G. Swisher, Wayne L. Hofstetter, Sushovan Guha, Michael T. Deavers, Asif Rashid, Dipen M. Maru

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The high interobserver variability in grading dysplasia in Barrett's esophagus demands a biomarker that can be applied in routine surgical pathology practice. Immunohistochemistry for phosphorylated histone H3 is a reliable marker of identifying mitotic figures and has not been evaluated in Barrett's esophagus-associated neoplastic lesions. We retrospectively studied the expression of phosphorylated histone H3 in 88 endoscopic biopsy samples of Barrett's esophagus without dysplasia (n19), indefinite for dysplasia (n11), low-grade dysplasia (n27), high-grade dysplasia (n19), or adenocarcinoma (n12) from a sample of 54 patients. The samples were included after consensus diagnosis of two gastrointestinal pathologists on the hematoxylin-eosin (HE)-stained sections. Anti-phosphorylated histone H3-labeled mitotic figures were counted per 10 consecutive high-power fields (HPFs) in three distinct regions: surface epithelium, upper 2/3, and lower 1/3 of the crypts. Anti-phosphorylated histone H3-labeled mitotic counts for the three compartments of the crypts and the total scores for Barrett's esophagus, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma were compared using the Mann-Whitney U test. For each compartment, the number of anti-phosphorylated histone H3-positive nuclei was higher in low-grade dysplasia than in Barrett's esophagus without dysplasia or indefinite for dysplasia (P0.001), but no difference was found between Barrett's esophagus without dysplasia and indefinite for dysplasia. High-grade dysplasia biopsies had significantly more anti-phosphorylated histone H3-labeled mitotic figures in the surface epithelium than the low-grade dysplasia (P0.001). Adenocarcinoma had higher anti-phosphorylated histone H3-labeled mitotic figures than the high-grade dysplasia (P0.001). Our data support the previous findings of expansion of the proliferative zone and importance of surface mitotic figure in the progression of Barrett's esophaguslow-grade dysplasia-high-grade dysplasia. In addition, phosphorylated histone H3 is a potential supportive marker to histology in differentiating low-grade dysplasia from indefinite for dysplasia and high-grade dysplasia from adenocarcinoma in the mucosal biopsy samples.

Original languageEnglish (US)
Pages (from-to)1612-1621
Number of pages10
JournalModern Pathology
Issue number12
StatePublished - Dec 2009


  • Adenocarcinoma
  • Barrett's esophagus
  • Mitotic figure
  • PHH3

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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