title: Phosphorylated histone H3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 expression in benign and atypical granular cell tumors.
abstract: BACKGROUND
  Granular cell tumors (GCTs) are classified as benign when none of the following features is present: spindling of the tumor cells, necrosis, diffuse pleomorphism, prominent nucleoli, high nuclear-cytoplasmic ratio, and mitotic rate >2 per 10 high-power fields. It has been suggested that a GCT be classified as atypical when 1 or 2 of these features are seen and as malignant when 3 or more of these are present. In our practice, we do not classify GCTs as malignant in the absence of metastasis.
  
  
  OBJECTIVE
  To compare immunohistochemical staining for phosphorylated histone H3 (PHH3), Ki-67 (MIB-1), p21, fatty acid synthase, and cleaved caspase-3 in histologically classified benign and atypical GCTs.
  
  
  METHODS
  We reviewed 25 cases of GCT from our archives and classified 14 as atypical based on histologic features. Immunohistochemical staining for PHH3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 was performed using standard methods. The number of positive cells for Ki-67, p21, and PHH3 was calculated in 10 consecutive high-power fields in a hot spot. Fatty acid synthase and cleaved caspase-3 cytoplasmic expression was graded from 1 to 3.
  
  
  RESULTS
  Ki-67 and PHH3 scores were significantly higher in atypical GCTs. The expression of p21, fatty acid synthase, and cleaved caspase-3 was not significantly different between atypical and benign GCTs.
  
  
  CONCLUSIONS
  This study shows that histologic features are reliable in identifying GCTs that have a higher proliferative potential as shown by higher immunoreactivity for Ki-67 and PHH3. These immunostains may help in classifying GCTs in cases where a thorough histologic evaluation is precluded by the small size of a biopsy specimen.
authors.affiliation: Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9073, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.forename: Jyoti P
authors.initials: JP
authors.lastname: Balani
authors.forename: Lonnie C
authors.initials: LC
authors.lastname: Roy
authors.forename: Robin H
authors.initials: RH
authors.lastname: Amirkhan
authors.forename: Mai P
authors.initials: MP
authors.lastname: Hoang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D003937:Diagnosis, Differential; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016586:Granular Cell Tumor / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D009336:Necrosis / Q000473:pathology; D010766:Phosphorylation; D012189:Retrospective Studies; D012983:Soft Tissue Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D019394:Ki-67 Antigen; D064429:Fatty Acid Synthases; D053148:Caspase 3