Clinicopathological and prognostic significance of stromal p16 and p53 expression in oral squamous cell carcinoma

Yusuke Amano; Masayo Hasegawa; Atsushi Kihara; Daisuke Matsubara; Noriyoshi Fukushima; Hiroshi Nishino; Yoshiyuki Mori; Kentaro Inamura; Toshiro Niki

doi:10.1016/j.anndiagpath.2025.152439

Clinicopathological and prognostic significance of stromal p16 and p53 expression in oral squamous cell carcinoma

Ann Diagn Pathol. 2025 Jan 15:75:152439. doi: 10.1016/j.anndiagpath.2025.152439. Online ahead of print.

Authors

Yusuke Amano¹, Masayo Hasegawa², Atsushi Kihara³, Daisuke Matsubara⁴, Noriyoshi Fukushima⁵, Hiroshi Nishino⁶, Yoshiyuki Mori⁷, Kentaro Inamura⁸, Toshiro Niki⁵

Affiliations

¹ Division of Tumor Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan; Department of Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan. Electronic address: [email protected].
² Department of Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan; Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University Saitama Medical Center, 1-847, Amanumacho, Omiya-ku, Saitama, Japan.
³ Division of Tumor Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan; Department of Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan; Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan.
⁴ Department of Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan; Department of Pathology, Faculty of medicine, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, Japan.
⁵ Department of Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan.
⁶ Department of Otolaryngology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan.
⁷ Department of Dentistry, Oral and Maxillofacial Surgery, Jichi Medical University Saitama Medical Center, 1-847, Amanumacho, Omiya, Saitama, Saitama, Japan.
⁸ Division of Tumor Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan; Department of Pathology, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, Japan; Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, Japan.

PMID: 39837151
DOI: 10.1016/j.anndiagpath.2025.152439

Abstract

The tumor microenvironment is highly heterogeneous and consists of neoplastic cells and diverse stromal components, including fibroblasts, endothelial cells, pericytes, immune cells, local and bone marrow-derived stromal stem and progenitor cells, and the surrounding extracellular matrix. Although the significance of p16 and p53 has been reported in various tumor types, their involvement in the stromal cells of oral squamous cell carcinoma (OSCC) remains unclear. We performed immunohistochemical analyses of p16 and p53 expression in OSCC samples, Of the 116 samples, 74 showed p16-positive stromal cells, and 33 showed p53-positive stromal cells. Both p16 and p53 positivity were associated with an increased histological grade, lymphovascular invasion, an immature stromal pattern with abundant amorphous extracellular matrix material, infiltrative invasion patterns (Yamamoto Kohama classification-4C and 4D), and poor prognosis. Multivariate analyses identified p16 and p53 positivity in the stroma as independent prognostic factors for overall survival (P = 0.032 and P = 0.020, respectively); moreover, stromal p16 positivity correlated with stromal p53 positivity. These findings indicated that p16 and p53 stroma positivity may regulate OSCC tumor aggressiveness.

Keywords: Oral squamous cell carcinoma; Prognosis; Stromal pattern; p16; p53.