Phosphorylated histone H3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3 expression in benign and atypical granular cell tumors

Arch Pathol Lab Med. 2007 Jan;131(1):57-64. doi: 10.5858/2007-131-57-PHHKPF.

Abstract

Context: 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.

Design: 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Diagnosis, Differential
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Granular Cell Tumor / diagnosis
  • Granular Cell Tumor / genetics
  • Granular Cell Tumor / metabolism*
  • Granular Cell Tumor / pathology
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Immunohistochemistry / methods
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Male
  • Middle Aged
  • Mitosis
  • Necrosis / pathology
  • Phosphorylation
  • Retrospective Studies
  • Soft Tissue Neoplasms / diagnosis
  • Soft Tissue Neoplasms / genetics
  • Soft Tissue Neoplasms / metabolism*
  • Soft Tissue Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21
  • Histones
  • Ki-67 Antigen
  • Fatty Acid Synthases
  • Caspase 3