# Significance of P53-Binding Protein 1 as a Novel Molecular Histological Marker for Hypopharyngeal Squamous Neoplasms

## TL;DR

This study shows that 53BP1, a DNA repair protein, can help diagnose and predict outcomes in hypopharyngeal cancer by tracking its expression patterns in tumor cells.

## Contribution

The study identifies 53BP1 as a novel molecular marker for hypopharyngeal squamous cell carcinoma progression and prognosis.

## Key findings

- 53BP1 nuclear foci increase with the progression from non-tumorous to cancerous hypopharyngeal lesions.
- Aberrant 53BP1 expression correlates with tumor thickness and risk of metastasis in hypopharyngeal cancer.
- 53BP1 co-expression with Ki67 is significantly higher in tumors exceeding 1000 µm in depth.

## Abstract

The DNA damage response protein p53-binding protein 1 (53BP1) exhibits abnormal foci in the nucleus during carcinogenesis in various organs. However, the pathophysiological changes that occur during the carcinogenic process of hypopharyngeal squamous cell carcinoma remain unclear. This study revealed a stepwise increase in aberrant 53BP1 expression on the tumor surface during carcinogenesis. In addition, a significant difference in the co-expression of 53BP1 and Ki67 was observed on the tumor surface when the tumor thickness exceeded 1000 µm, which is considered the threshold at which the risk of lymph node metastasis and vascular invasion increases in hypopharyngeal cancer. These findings suggest that 53BP1 could be useful for the pathological diagnosis of hypopharyngeal cancer and for predicting the prognosis of patients with this disease.

The DNA damage response protein p53-binding protein 1 (53BP1) accumulates and forms foci at double-strand DNA breaks, indicating the extent of DNA instability. However, the potential role of 53BP1 as a molecular biomarker for hypopharyngeal squamous cell carcinoma (HPSCC) diagnosis remains unknown. Here, we evaluated the potential of immunofluorescence-based analysis of 53BP1 expression to differentiate the histology of hypopharyngeal neoplasms. A total of 125 lesions from 39 surgically or endoscopically resected specimens from patients with HPSCC was histologically evaluated. 53BP1 expression in the nucleus was examined using immunofluorescence. The number of 53BP1 nuclear foci increased with the progression from non-tumorous to low-grade dysplasia, high-grade dysplasia, and squamous cell carcinoma. Unstable 53BP1 expression served as an independent factor for distinguishing lesions that required intervention. Colocalization of 53BP1 foci in proliferating cells, as assessed by Ki67, was increased in tumors ≥ 1000 µm in depth compared to those <1000 µm in depth at the tumor surface. Hence, the expression patterns of nuclear 53BP1 foci were associated with the progression of hypopharyngeal neoplasms. These findings suggest that 53BP1 could serve as an ancillary marker to support histological diagnosis and predict the factors that influence prognosis in patients with HPSCC.