Expression of P53 and Prognosis in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Abstract

Introduction: Mutation of TP53 is the most common genetic abnormality in head and neck squamous cell carcinoma (HNSCC) and results in an accumulation and expression of p53 protein in tumor cells. Disruptive TP53 mutations are consistently associated with poor prognosis but correlations of p53 expression with mutation or prognosis have been variable and the usefulness of p53 as a target for immunotherapy is unknown. Favorable prognosis is associated with the accumulation of T lymphocytes (TILs) in the tumor microenvironment and an immune response to p53 has been suggested by demonstration of antibodies to p53 and p53-restricted cytotoxic cells in patients with HNSCC. To investigate if p53 expression is related to accumulation of TILs, p53 expression was measured in a prospective cohort of patients with HNSCC and correlations with TILs and prognosis were determined.Methods: Studied were 534 previously untreated patients (n) with oral cavity (273), oropharynx (158), larynx (81) or hypopharynx ( 22) cancers. Expression of p53, p21, and p16 and levels of T cell infiltrates (CD4, CD8, FoxP3) were assessed by immunohistology in tissue microarrays from biopsy specimens. HPV testing by routine pathology was available for 401 patients. Associations with clinical variables were tested using Kruskal-Wallis tests (p53, p21) or Chi-square test (p16). Kaplan-Meier and Cox regression methods were used to evaluate univariable and multivariable associations of protein expression with TIL levels and overall survival (OS) and disease specific survival (DSS) after adjusting for known prognostic factors. Median follow up was 44 months.

USP28: Oncogene or Tumor Suppressor? A Unifying Paradigm for Squamous Cell Carcinoma

“…SCCs present one of the genetically most complex tumors, as they vary dramatically between patients in terms of the occurrence of tumor drivers [70]. Predominantly recurring genetic alterations are found in p53; these are more frequent compared to other tumor entities [71,72]. Copy number alterations of SOX2, PDGFRA, or FGFR1, along with deletions of tumor-suppressor CDKN2A, are frequently reported for SCC.…”

“…As indicated, recent reports have demonstrated that USP28 stabilizes and regulates the activity of p53, acting as tumor suppressor [18,44] [45,105]. SCC tumors frequently suffer p53 mutations or genetic alterations [71,72]. In tumors with functional mutations in p53, the stabilization of p53 by USP28 may even prove detrimental for cancer patients, because mutant p53 is considered an oncogene.…”

CDK7 Predicts Worse Outcome in Head and Neck Squamous-Cell Cancer

“…Tumors harboring high-risk mutations showed worse outcomes [13]. Nonetheless, an IHC study carried out to evaluate the association of p53 protein expression to clinicopathological features of an HNSCC cohort could not prove prognostic implications [14].…”