Inverse correlation between microtubule-associated protein 1A/1B-light chain 3 and p62/sequestosome-1 expression in the progression of cutaneous squamous cell carcinoma

J Dermatol. 2014 Apr;41(4):311-5. doi: 10.1111/1346-8138.12439.

Abstract

The expression of autophagy-related markers has occasionally been reported to correlate with the clinical stage of disease in patients with solid cancer, indicating autophagy activation. However, there have been no such reports for cutaneous squamous cell carcinoma. In this study, we investigated the expression levels of two autophagy-related markers, microtubule-associated protein IA/IB light chain 3 (LC3) and p62/sequestosome-1 (p62), in cutaneous squamous cell carcinoma specimens and assessed their correlation to clinicopathological factors in patients with this type of cancer. As a marker of the autophagosome, LC3 expression increases with autophagosome formation/accumulation, whereas p62 expression decreases due to selective degradation via autophagy. We performed immunostaining for LC3 and p62 in 50 cutaneous squamous cell carcinoma specimens obtained from patients treated by surgical resection, counted the number of cells that showed positive staining, and calculated the percentage of positive cells per low-power microscopic field. We next investigated the correlations between the expression levels of these markers and various clinicopathological factors. The results indicated that LC3 expression increased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.046). By contrast, the expression of p62 decreased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.001). These results suggest that autophagy becomes activated during disease progression in patients with cutaneous squamous cell carcinoma.

Keywords: autophagy; cutaneous squamous cell carcinoma; lysosomal-associated membrane protein 1; microtubule-associated protein IA/IB light chain 3; p62/sequestosome-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Autophagy
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Lysosomal Membrane Proteins / metabolism
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Sequestosome-1 Protein
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • LAMP1 protein, human
  • Lysosomal Membrane Proteins
  • MAP1LC3A protein, human
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein