Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery

Tami Yu-Yu Lin; Kelly Yi Ping Liu; Rachel Novack; Pushwant S Mattu; Tony L Ng; Lynn N Hoang; Eitan Prisman; Catherine F Poh; Yen Chen Kevin Ko

doi:10.1016/j.modpat.2024.100614

Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery

Mod Pathol. 2024 Sep 10;37(12):100614. doi: 10.1016/j.modpat.2024.100614. Online ahead of print.

Authors

Tami Yu-Yu Lin¹, Kelly Yi Ping Liu², Rachel Novack³, Pushwant S Mattu³, Tony L Ng¹, Lynn N Hoang¹, Eitan Prisman⁴, Catherine F Poh⁵, Yen Chen Kevin Ko⁶

Affiliations

¹ Department of Anatomical Pathology, Vancouver General Hospital, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
² Department of Oral Medical Biological Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada; Department of Integrative Oncology, BC Cancer, Vancouver, British Columbia, Canada; School of Biomedical Engineering, Faculty of Applied Science and Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
³ Department of Anatomical Pathology, Vancouver General Hospital, Vancouver, BC, Canada.
⁴ Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
⁵ Department of Oral Medical Biological Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada; Department of Integrative Oncology, BC Cancer, Vancouver, British Columbia, Canada.
⁶ Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Oral Medical Biological Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada; Department of Pathology, BC Cancer, Vancouver, British Columbia, Canada. Electronic address: kevin.ko@ubc.ca.

PMID: 39265952
DOI: 10.1016/j.modpat.2024.100614

Abstract

Most (60%-80%) of the oral cavity invasive squamous cell carcinoma (OSCC) demonstrate molecular alterations in TP53. The presence of TP53 mutations in multiple organ systems has been associated with a more aggressive clinical course. This study aimed to classify OSCC into p53 wild-type OSCC and p53-abnormal OSCC using p53 immunohistochemistry and to determine if abnormal p53 status correlates with a higher risk of lymph node metastasis at the time of surgery. A total of 101 patients with OSCC resection and cervical lymph node dissection were identified. p53 immunohistochemistry was performed for all cases and scored into p53 wild-type (p53-HPV: midepithelial/basal sparing, markedly reduced [null-like]/basal sparing; p53-conventional: scattered basal, patchy basal/parabasal) and p53-abnormal (overexpression basal/parabasal only, overexpression basal/parabasal to diffuse, null, and cytoplasmic) patterns. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization were used to confirm the HPV status in cases showing midepithelial/basal sparing or markedly reduced (null-like)/basal sparing pattern. Logistic regression analysis was performed to investigate the association of p53 status, tumor size, depth of invasion, and pT stage against lymph node status. We identified 22 cases with p53 wild-type patterns (16 p53-conventional, 6 p53-HPV) and 79 cases with p53-abnormal patterns. Two of 22 p53 wild-type cases had positive lymph nodes (1 p53-conventional, 1 p53-HPV), whereas 40 of 79 p53-abnormal cases had positive lymph nodes (P < .001). Multivariate analysis showed that p53-abnormal pattern was an independent risk factor associated with positive node(s) with an odds ratio of 8.12 (95% CI, 2.10-53.78; P = .008). p53-Abnormal OSCCs were significantly more likely to be associated with positive lymph node status than p53 wild-type OSCCs at the time of surgery. Further investigation with long-term follow-up is required to determine its clinical application before surgery planning.

Keywords: TP53; abnormal p53; node metastasis; oral cavity squamous cell carcinoma; p53.