Immunohistochemical assessment of chromatin licensing and DNA replication factor 1, geminin, and γ-H2A.X in oral epithelial precursor lesions and squamous cell carcinoma

J Oral Pathol Med. 2019 Nov;48(10):888-896. doi: 10.1111/jop.12925. Epub 2019 Aug 16.

Abstract

Background: Carcinogenesis occurs when the cell cycle is compromised. Chromatin licensing and DNA replication factor 1, geminin, and γ-H2A histone family member X are expressed in cells in G1 phase, S/G2 /M phases, and apoptosis, respectively, and these three markers may be useful for histological evaluation of malignant lesions. Here, we aimed to identify cell cycle phases and apoptosis using immunohistochemistry in oral epithelial precursor lesions and oral squamous cell carcinoma.

Methods: Chromatin licensing and DNA replication factor 1, geminin, and γ-H2A histone family member X expression levels were immunohistochemically examined in tissue specimens from 55 patients with oral epithelial precursor lesions and 50 patients with oral squamous cell carcinoma. Associations of clinicopathological variables with marker expression were assessed.

Results: Chromatin licensing and DNA replication factor 1 was expressed in the prickle cell layer of oral epithelial precursor lesions and many carcinoma cells of oral squamous cell carcinoma. Geminin reactivity was widely distributed in high-grade dysplasia and oral squamous cell carcinoma rather than low-grade or no dysplastic cases. γ-H2A histone family member X was expressed in the superficial layer of oral epithelial precursor lesions and scattered carcinoma cells of oral squamous cell carcinoma. In oral squamous cell carcinoma, lower geminin expression was observed in recurrent cases. Geminin and γ-H2A histone family member X were associated with the degree of differentiation and mode of invasion.

Conclusion: Chromatin licensing and DNA replication factor 1, geminin, and γ-H2A histone family member X expression levels were correlated with oral carcinogenesis; these markers were associated with clinicopathological behaviors in oral squamous cell carcinoma.

Keywords: chromatin licensing and DNA replication factor 1; geminin; oral epithelial precursor lesions; oral squamous cell carcinoma; γ-H2A histone family member X.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Proteins / metabolism*
  • Female
  • Geminin / metabolism*
  • Histones / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • CDT1 protein, human
  • Cell Cycle Proteins
  • Geminin
  • Histones