Correlation between p53 staining and TP53 mutation status in 60 patients with oral squamous cell carcinoma

doi:10.19438/j.cjoms.2025.03.006

Abstract

Abstract: PURPOSE: This study aimed to investigate the correlation between p53 staining patterns and TP53 mutation status in oral squamous cell carcinoma(OSCC), as well as their associations with clinicopathologic features. METHODS: Tissue samples from 60 OSCC patients were analyzed using whole-exome sequencing and immunohistochemical staining with p53 antibodies (MX008 and YN01766m). TP53 mutation status and p53 staining patterns (Null, overexpression [OE], and wild type[WT]) were compared with clinicopathologic features. Correlations between p53 staining patterns and TP53 mutation status were evaluated. GraphPad Prism 8 software package was used for data analysis. RESULTS: TP53 was the most frequently mutated gene in OSCC, with mutations significantly associated with higher pTNM stage, DOI, and PNI, and correlated with poor prognosis in public datasets. The Null pattern exhibited the highest sensitivity in detecting loss-of-function (LOF) mutations, while OE pattern predicted gain-of-function (GOF) mutations and showed clinical value for patient stratification. Both antibodies had similar performance in detecting and matching TP53 mutation status. CONCLUSION: TP53 is the most common mutation in OSCC,and its mutation is associated with adverse clinicopathological features and poor prognosis. p53 staining is sensitive to LOF mutations and is expected to be a biomarker of GOF mutations, providing a cost-effective method for patient stratification and targeted therapy.

Key words: Oral squamous cell carcinoma, TP53 mutation, p53 staining pattern, LOF mutation, GOF mutation, Clinicopathologic features

CLC Number:

R739.8

Liu Yu, Miao Keyan, Hu Yuhua, Wu Yue, Feng Guanying, Xia Ronghui, Yang Xi. Correlation between p53 staining and TP53 mutation status in 60 patients with oral squamous cell carcinoma[J]. China Journal of Oral and Maxillofacial Surgery, 2025, 23(3): 244-252.

References

[1] Martínez-Jiménez F, Muiños F, Sentís I, et al.A compendium of mutational cancer driver genes[J]. Nat Rev Cancer, 2020, 20(10): 555-572.
[2] Liu Y, Gu W.The complexity of p53-mediated metabolic regulation in tumor suppression[J]. Semin Cancer Biol, 2022, 85: 4-32.
[3] Zhou Y, Jin J, Ji Y, et al.TP53 missense mutation reveals gain-of-function properties in small-sized KRAS transformed pancreatic ductal adenocarcinoma[J]. J Transl Med, 2023, 21(1): 872-887.
[4] Qayoom H, Haq BU, Sofi S, et al.Targeting mutant p53: a key player in breast cancer pathogenesis and beyond[J]. Cell Commun Signal, 2024, 22(1): 484-497.
[5] Wang Z, Burigotto M, Ghetti S, et al.Loss-of-function but not gain-of-function properties of mutant TP53 are critical for the proliferation, survival, and metastasis of a broad range of cancer cells[J]. Cancer Discov, 2024, 14(2): 362-379.
[6] Anderson SA, Bartow BB, Harada S, et al.p53 protein expression patterns associated with TP53 mutations in breast carcinoma[J]. Breast Cancer Res Treat, 2024, 207(1): 213-222.
[7] Novack R, Zhang L, Hoang LN, et al.Abnormal p53 immunohistochemical patterns shed light on the aggressiveness of oral epithelial dysplasia[J]. Mod Pathol, 2023, 36(7): 100153.
[8] Chen S, Zhou Y, Chen Y, et al.fastp: an ultra-fast all-in-one FASTQ preprocessor[J]. Bioinformatics, 2018, 34(17): i884-i890.
[9] Li H, Durbin R.Fast and accurate long-read alignment with Burrows-Wheeler transform[J]. Bioinformatics, 2010, 25(5): 1754-1760.
[10] Li H, Handsaker B, Wysoker A, et al.The sequence alignment/map format and SAMtools[J]. Bioinformatics, 2009, 25(16): 2078-2079.
[11] McKenna A, Hanna M, Banks E, et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data[J]. Genome Res, 2010, 20(9): 1297-1303.
[12] Wang K, Li M, Hakonarson H.ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data[J]. Nucleic Acids Res, 2010, 38(16): e164.
[13] Cibulskis K, Lawrence MS, Carter SL, et al.Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples[J]. Nat Biotechnol, 2013, 31(3): 213-219.
[14] Boeva V, Popova T, Bleakley K, et al.Control-FREEC: a tool for assessing copy number and allelic content using next-generation sequencing data[J]. Bioinformatics, 2012, 28(3): 423-425.
[15] Layer RM, Chiang C, Quinlan AR, et al. LUMPY: a probabilistic framework for structural variant discovery[J]. Genome Biol, 2014, 15(6): R84.
[16] Johnson DE, Burtness B, Leemans CR, et al.Head and neck squamous cell carcinoma[J]. Nat Rev Dis Primers, 2020, 6(1): 92-140.
[17] Köbel M, Piskorz AM, Lee S, et al.Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma[J]. J Pathol Clin Res, 2016, 2(4): 247-258.
[18] Hwang HJ, Nam SK, Park H, et al.Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer[J]. J Pathol Transl Med, 2020, 54(5): 378-386.
[19] Sakamoto I, Kagami K, Nozaki T, et al.p53 immunohistochemical staining and TP53 gene mutations in endometrial cancer: does null pattern correlate with prognosis?[J]. Am J Surg Pathol, 2023, 47(10): 1144-1150.
[20] Schoop I, Maleki SS, Behrens HM, et al.p53 immunostaining cannot be used to predict TP53 mutations in gastric cancer: results from a large Central European cohort[J]. Hum Pathol, 2020, 105: 53-66.
[21] Shirole NH, Pal D, Kastenhuber ER, et al.TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions[J]. Elife, 2017, 6: e25532.
[22] Jin Y, Zhao X, Song X, et al.The high expression of p53 is predictive of poor survival rather TP53 mutation in esophageal squamous cell carcinoma[J]. J Oncol, 2023, 2023: 3801526.
[23] Babamohamadi M, Babaei E, Ahmed Salih B, et al.Recent findings on the role of wild-type and mutant p53 in cancer development and therapy[J]. Front Mol Biosci, 2022, 9: 903075.
[24] Brosh R, Rotter V.When mutants gain new powers: news from the mutant p53 field[J]. Nat Rev Cancer, 2009, 9(10): 701-713.
[25] Arnold M, Soerjomataram I, Ferlay J, et al.Global incidence of oesophageal cancer by histological subtype in 2012[J]. Gut, 2015, 64(3): 381-387.
[26] Allemani C, Matsuda T, Di Carlo V, et al.Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries[J]. Lancet, 2018, 391(10125): 1023-1075.
[27] Leroy B, Ballinger ML, Baran-Marszak F, et al.Recommended guidelines for validation, quality control, and reporting of TP53 variants in clinical practice[J]. Cancer Res, 2017, 77(6): 1250-1260.
[28] Chien CY, Huang CC, Cheng JT, et al.The clinicopathological significance of p53 and p21 expression in squamous cell carcinoma of hypopharyngeal cancer[J]. Cancer Lett, 2003, 201(2): 217-223.
[29] Li XM, Song X, Zhao XK, et al.The alterations of cytokeratin and vimentin protein expressions in primary esophageal spindle cell carcinoma[J]. BMC Cancer, 2018, 18(1): 356-368.
[30] Yang X, Tian X, Wu K, et al.Prognostic impact of perineural invasion in early stage oral tongue squamous cell carcinoma: results from a prospective randomized trial[J]. Surg Oncol, 2018, 27(2): 123-128.