title: Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.
abstract: 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 (n=19), indefinite for dysplasia (n=11), low-grade dysplasia (n=27), high-grade dysplasia (n=19), or adenocarcinoma (n=12) 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 (P<0.001), 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 (P<0.001). Adenocarcinoma had higher anti-phosphorylated histone H3-labeled mitotic figures than the high-grade dysplasia (P<0.001). Our data support the previous findings of expansion of the proliferative zone and importance of surface mitotic figure in the progression of Barrett's esophagus-low-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.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Goodarzi
authors.forename: Arlene M
authors.initials: AM
authors.lastname: Correa
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Hofstetter
authors.forename: Sushovan
authors.initials: S
authors.lastname: Guha
authors.forename: Michael T
authors.initials: MT
authors.lastname: Deavers
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.forename: Dipen M
authors.initials: DM
authors.lastname: Maru
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002467:Cell Nucleus / Q000737:chemistry; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006657:Histones / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009092:Mucous Membrane / Q000737:chemistry / Q000473:pathology; D009367:Neoplasm Staging; D010766:Phosphorylation; D011230:Precancerous Conditions / Q000737:chemistry* / Q000473:pathology; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones