Filaggrin expression via immunohistochemistry in basal cell carcinoma and squamous cell carcinoma

J Cutan Pathol. 2021 Jul;48(7):877-883. doi: 10.1111/cup.13975. Epub 2021 Feb 18.

Abstract

Background: Filaggrin is a protein integral to the structure and function of the epidermis. Filaggrin (FLG) loss-of-function (LOF) mutations are common and increase the risk of developing atopic dermatitis (AD) and ichthyosis vulgaris (IV). Epidemiologic data suggest a link between skin cancer and AD. We examined if FLG staining pattern can be used to characterize cutaneous squamous cell carcinomas (SCC), basal cell carcinomas (BCC), and reactive squamous epithelium.

Methods: Tissue microarrays (TMAs) were created from 196 cases of formalin-fixed paraffin-embedded (FFPE) SCC and 144 BCC cases. TMAs and sections of reactive squamous epithelium were stained with optimized anti-FLG antibody and evaluated for FLG expression (normal, abnormal, or negative).

Results: FLG was absent in poorly differentiated (PD) compared to well-differentiated (WD) SCC (P < .0001) and moderately-differentiated (MD) (P = .0231) SCC, and in MD compared to WD SCC (P = .0099). Abnormal staining was significantly increased in PD compared to WD cases (P = .0039) and in MD compared to WD cases (P = .0006). Most BCC did not exhibit FLG expression (P < .05). Reactive squamous epithelium demonstrated normal, but exaggerated FLG expression.

Conclusions: Our findings demonstrate the differences in FLG expression patterns in types of keratinocyte carcinomas and their mimickers.

Keywords: atopic dermatitis; basal cell carcinoma; filaggrin; ichthyosis vulgaris; squamous cell carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Carcinoma, Basal Cell / diagnosis*
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics
  • Cell Differentiation / genetics
  • Dermatitis, Atopic / epidemiology
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / metabolism
  • Dermatitis, Atopic / pathology
  • Epidermis / metabolism
  • Epidermis / pathology
  • Female
  • Filaggrin Proteins
  • Genetic Predisposition to Disease
  • Humans
  • Ichthyosis Vulgaris / epidemiology
  • Ichthyosis Vulgaris / genetics
  • Ichthyosis Vulgaris / metabolism
  • Ichthyosis Vulgaris / pathology
  • Immunohistochemistry / methods*
  • Intermediate Filament Proteins / genetics*
  • Intermediate Filament Proteins / immunology
  • Loss of Function Mutation / genetics
  • Male
  • Skin Neoplasms / pathology*
  • Staining and Labeling / methods
  • Tissue Array Analysis / methods

Substances

  • FLG protein, human
  • Filaggrin Proteins
  • Intermediate Filament Proteins

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