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

Author:

Kawasaki-Inomata Hiroko1ORCID,Tabuchi Maiko12,Norimatsu Kiyuu3,Honda Tetsuro4,Matsuda Katsuya5ORCID,Hashiguchi Keiichi1ORCID,Yamaguchi Naoyuki1,Nishi Hideaki6,Kumai Yoshihiko6,Nakashima Masahiro5ORCID,Miyaaki Hisamitsu1,Nakao Kazuhiko17,Akazawa Yuko2

Affiliation:

1. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan

2. Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan

3. Department of Rheumatology, National Hospital Organization Ureshino Medical Center, Saga 843-0393, Japan

4. Medical Education Development Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan

5. Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki 852-8523, Japan

6. Department of Otolaryngology, Head and Neck Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan

7. Department of Gastroenterology, Sasebo City General Hospital, Nagasaki 857-8511, Japan

Abstract

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.

Funder

Network-type Joint Usage/Research Center for Radiation Disaster Medical Science

Publisher

MDPI AG

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