Alteration of p53-binding protein 1 expression during skin carcinogenesis: association with genomic instability

Yuki Naruke1, Masahiro Nakashima, Keiji Suzuki

  • 1Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki Unviersity Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.

Cancer Science
|April 3, 2008
PubMed

Insights

Genomic instability (GIN) is crucial in skin cancer progression. 53BP1 nuclear foci indicate DNA damage response activation, serving as a marker for GIN and malignant potential in skin tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Epidermal cells face genotoxic agents, triggering DNA damage response (DDR) to maintain genomic integrity.
  • Defective DDR leads to genomic instability (GIN), a key factor in cancer development.
  • 53BP1 protein localizes to DNA double-strand breaks (DSB) and forms nuclear foci, acting as a marker for GIN.

Purpose of the Study:

  • To analyze genomic instability levels in various human skin tumors using 53BP1 as a biomarker.
  • To investigate the role of 53BP1 and DDR in the progression of skin carcinogenesis.
  • To evaluate 53BP1 immunofluorescence as a potential marker for estimating the malignant potential of skin tumors.

Main Methods:

  • Immunofluorescence studies were performed to detect 53BP1 nuclear foci.
  • 53BP1 levels were analyzed in 56 skin tumors, including seborrheic keratosis, actinic keratosis, Bowen's disease, squamous cell carcinoma, and basal cell carcinoma.
  • Nuclear accumulation of p53 was also assessed in invasive cancers.

Main Results:

  • A significant number of 53BP1 nuclear foci were observed in human skin tumors, indicating constitutive DDR activation.
  • Actinic keratosis, a precancerous lesion, showed high 53BP1 immunoreactivity, suggesting GIN induction at this stage.
  • Invasive cancers displayed intense, abnormal 53BP1 staining and p53 accumulation, pointing to disrupted DDR and high GIN.

Conclusions:

  • Genomic instability plays a critical role in the progression of skin carcinogenesis.
  • 53BP1 nuclear foci serve as a reliable cytological marker for endogenous DSB and GIN.
  • 53BP1 detection via immunofluorescence can be a valuable histological tool for assessing the malignant potential of skin tumors.

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