Evaluation of P53 immunostaining in patients with cutaneous melanoma

Meevassana,Jiraroch; Mittrakulkij,Chanya; Toworrakul,Ponteera; Saensuk,Wantamol; Kamolratanakul,Supitcha; Siritientong,Tippawan; Ruangritchankul,Komkrit; Kitkumthorn,Nakarin

doi:10.3892/br.2023.1696

Evaluation of P53 immunostaining in patients with cutaneous melanoma

Authors:
- Jiraroch Meevassana
- Chanya Mittrakulkij
- Ponteera Toworrakul
- Wantamol Saensuk
- Supitcha Kamolratanakul
- Tippawan Siritientong
- Komkrit Ruangritchankul
- Nakarin Kitkumthorn
View Affiliations

Affiliations: Center of Excellence in Burn and Wound Care, Chulalongkorn University, Bangkok 10330, Thailand, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand, Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand, Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand
Published online on: November 22, 2023 https://doi.org/10.3892/br.2023.1696
Article Number: 8
Copyright: © Meevassana et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

P53 is a tumor suppressor gene that is mutated in numerous types of cancer. The aim of the present study was to determine the frequency of this mutation in cutaneous melanomas and to conduct clinicopathological characteristics and clinical outcome association analyses with the P53 mutation. P53 immunohistochemical staining was used as a surrogate marker for P53 mutation analysis to assess P53 status. In the present study, 50 pathological samples of cutaneous melanoma from 2012 to 2018 at Chulalongkorn University (Bangkok, Thailand), were subjected to anti‑P53 immunohistochemistry, followed by an examination of the association between P53 statuses and clinical and pathological characteristics, along with clinical outcomes. A positive staining for anti‑P53 antibody was detected in 30% of patients (15/50) with cutaneous melanomas. Positivity was significantly associated with female sex, nodular histological subtype and Breslow level 4. Cox regression analysis revealed that an age >65.5 years and Breslow grade 4 disease were associated with mortality. The Kaplan‑Meier curve revealed a shorter duration of recurrence time in the P53 mutation than P53 wild type. In the present study, P53 mutations in specific cases of cutaneous melanoma were identified. Notably, patients who were older and/or had a Breslow score of 4 exhibited an increased risk of mortality. These findings suggested the potential involvement of P53 mutations in cutaneous melanoma, highlighting the necessity for further investigations to improve understanding of their roles.

View Figures

View References

1	Hassel JC and Enk AH: Melanoma. In: Kang S, Amagai M, Bruckner AL, Enk AH, Margolis DJ, McMichael AJ and Orringer JS (eds). Fitzpatrick's Dermatology. 9th edition. McGraw Hill, New York, NY, pp1982-2011, 2019.
2	Smoller BR: Histologic criteria for diagnosing primary cutaneous malignant melanoma. Mod Pathol. 19 (Suppl 2):S34–S40. 2006.PubMed/NCBI View Article : Google Scholar
3	Bandarchi B, Ma L, Navab R, Seth A and Rasty G: From melanocyte to metastatic malignant melanoma. Dermatol Res Pract. 2010(583748)2010.PubMed/NCBI View Article : Google Scholar
4	Liu Y and Sheikh MS: Melanoma: Molecular pathogenesis and therapeutic management. Mol Cell Pharmaco. 6(228)2014.PubMed/NCBI
5	Loureiro JB, Abrantes M, Oliveira PA and Saraiva L: P53 in skin cancer: From a master player to a privileged target for prevention and therapy. Biochim Biophys Acta Rev Cancer. 1874(188438)2020.PubMed/NCBI View Article : Google Scholar
6	Wiriyakulsit N, Klomkleang P, Sornda T and Kaewkong W: Melanoma: Incidence among the thai population and the use of a molecular understanding of this cancer to improve the strategy of targeted therapy. Thai Cancer J. 41:134–150. 2021.
7	Sullivan KD, Galbraith MD, Andrysik Z and Espinosa JM: Mechanisms of transcriptional regulation by p53. Cell Death Differ. 25:133–143. 2018.PubMed/NCBI View Article : Google Scholar
8	Meevassana J, Anothaisatapon K, Subbalekha S, Kamolratanakul S, Siritientong T, Ruangritchankul K, Pungrasami P, Hamill KJ, Angsapatt A and Kitkumthorn N: BRAF V600E immunohistochemistry predicts prognosis of patients with cutaneous melanoma in Thai population. Plast Reconstr Surg Glob Open. 10(e4605)2022.PubMed/NCBI View Article : Google Scholar
9	Ascierto PA, Kirkwood JM, Grob JJ, Simeone E, Grimaldi AM, Maio M, Palmieri G, Testori A, Marincola FM and Mozzillo N: The role of BRAF V600 mutation in melanoma. J Transl Med. 10(85)2012.PubMed/NCBI View Article : Google Scholar
10	Shadfan M, Lopez-Pajares V and Yuan ZM: MDM2 and MDMX: Alone and together in regulation of p53. Transl Cancer Res. 1:88–89. 2012.PubMed/NCBI
11	Rivlin N, Brosh R, Oren M and Rotter V: Mutations in the p53 tumor suppressor gene: Important milestones at the various steps of tumorigenesis. Genes Cancer. 2:466–474. 2011.PubMed/NCBI View Article : Google Scholar
12	Zhu G, Pan C, Bei JX, Li B, Liang C, Xu Y and Fu X: Mutant p53 in cancer progression and targeted therapies. Front Oncol. 10(595187)2020.PubMed/NCBI View Article : Google Scholar
13	Yemelyanova A, Vang R, Kshirsagar M, Lu D, Marks MA, Shih IeM and Kurman RJ: Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: An immunohistochemical and nucleotide sequencing analysis. Mod Pathol. 24:1248–1253. 2011.PubMed/NCBI View Article : Google Scholar
14	Singh N, Piskorz AM, Bosse T, Jimenez-Linan M, Rous B, Brenton JD, Gilks CB and Köbel M: p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies. J Pathol. 250:336–345. 2020.PubMed/NCBI View Article : Google Scholar
15	Keung EZ and Gershenwald JE: The eighth edition American joint committee on cancer (AJCC) melanoma staging system: implications for melanoma treatment and care. Expert Rev Anticancer Ther. 18:775–784. 2018.PubMed/NCBI View Article : Google Scholar
16	Zerp SF, van Elsas A, Peltenburg LT and Schrier PI: p53 mutations in human cutaneous melanoma correlate with sun exposure but are not always involved in melanomagenesis. Br J Cancer. 79:921–926. 1999.PubMed/NCBI View Article : Google Scholar
17	Hocker T and Tsao H: Ultraviolet radiation and melanoma: A systematic review and analysis of reported sequence variants. Hum Mutat. 28:578–588. 2007.PubMed/NCBI View Article : Google Scholar
18	Kim DW, Haydu LE, Joon AY, Bassett RL Jr, Siroy AE, Tetzlaff MT, Routbort MJ, Amaria RN, Wargo JA, McQuade JL, et al: Clinicopathological features and clinical outcomes associated with TP53 and BRAF^Non-V600 mutations in cutaneous melanoma patients. Cancer. 123:1372–1381. 2017.PubMed/NCBI View Article : Google Scholar
19	Rusu S, Verocq C, Trepant AL, Maris C, De Nève N, Blanchard O, Van Campenhout C, De Clercq S, Rorive S, Cotoi OS, et al: Immunohistochemistry as an accurate tool for the assessment of BRAF V600E and TP53 mutations in primary and metastatic melanoma. Mol Clin Oncol. 15(270)2021.PubMed/NCBI View Article : Google Scholar
20	Celesia A, Franzò M, Di Liberto D, Lauricella M, Carlisi D, D'Anneo A, Notaro A, Allegra M, Giuliano M and Emanuele S: Oncogenic BRAF and p53 interplay in melanoma cells and the effects of the HDAC inhibitor ITF2357 (Givinostat). Int J Mol Sci. 24(9148)2023.PubMed/NCBI View Article : Google Scholar
21	Tsai S, Balch C and Lange J: Epidemiology and treatment of melanoma in elderly patients. Nat Rev Clin Oncol. 7:148–152. 2010.PubMed/NCBI View Article : Google Scholar
22	Iglesias-Pena N, Paradela S, Tejera-Vaquerizo A, Boada A and Fonseca E: Cutaneous melanoma in the elderly: Review of a growing problem. Actas Dermosifiliogr (Engl Ed). 110:434–447. 2019.PubMed/NCBI View Article : Google Scholar
23	Jenkins RW and Fisher DE: Treatment of advanced melanoma in 2020 and beyond. J Invest Dermatol. 141:23–31. 2021.PubMed/NCBI View Article : Google Scholar
24	Box NF, Vukmer TO and Terzian T: Targeting p53 in melanoma. Pigment Cell Melanoma Res. 27:8–10. 2014.PubMed/NCBI View Article : Google Scholar