Effect of LMP-1 and mutant p53 on the Prognosis of Undifferentiated Type of Nasopharyngeal Carcinoma

Atikah Atikah, Udadi Sadhana, Ika Pawitra Miranti, Dik Puspasari, Vega Karlowee

Abstract


Undifferentiated carcinoma is a subtype of NPC with a higher EBV antibody titer than healthy people. The carcinogenic effect of EBV involves LMP-1 associated with poor prognosis, and mutant p53 predicts tumor recurrence. This study aims to assess the effect of LMP-1 and mutant p53 on the prognosis of NPC patients. 40 paraffin blocks were stained with LMP-1 and p53 mutant. LMP-1 was positive when the cytoplasm and tumor cell membranes were brown, and mutant p53 was positive for the brown tumor cell nucleus. Pearson correlation test was performed. Most respondents were in the age group > 40 years, males, regional lymph node involvement (N) in group N1, and no metastasis (M). The expression levels of LMP-1 and mutant p53 were strongly positive. The study showed the correlation between LMP-1 with age (p 0.327), gender (p 0.599), category N (p 0.512), category M (p 0.019) and the correlation between mutant p53 with age (p 0.329), gender (p 0.981), category N (p 0.013), category M (p 0.705). LMP-1 expression with mutant p53 (p 0.760). It can be concluded that LMP-1 and mutant p53 could be used as prognostic factors in NPC patients.


Keywords


LMP-1; Nasopharyngeal Carcinoma; p53 Mutant; Prognosis

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Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M. International Agency for Research on Cancer 2020. Glob Cancer Obs Cancer Today. 2020;419:1-2. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.

El-Naggar AK, Chan JKC, Grandis JR, Takata T SP. IARC Publications Website - WHO Classification of Head and Neck Tumours. 2017. https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Head-And-Neck-Tumours-2017%0Ahttp://publications.iarc.fr/Book-And-Report-Series/Who-Iarc-Classification-Of-Tumours.

Tabuchi K, Nakayama M, Nishimura B, Hayashi K, Hara A. Early Detection of Nasopharyngeal Carcinoma. Int J Otolaryngol. 2011;2011. https://doi.org/10.1155/2011/638058

Zeng M-S, Zeng Y-X. Pathogenesis and Etiology of Nasopharyngeal Carcinoma. 2010:9-25. doi:10.1007/978-3-540-92810-2_2

Adham M, Kurniawan AN, Muhtadi AI, Roezin A, Hermani B, Gondhowiarjo S, Tan IB, Middeldorp JM. Nasopharyngeal Carcinoma in Indonesia: Epidemiology, Incidence, Signs, and Symptoms at Presentation. Chin J Cancer. 2012;31(4):185-196. https://doi.org/10.5732/cjc.011.10328

Zhang L, Chen QY, Liu H, Tang LQ, Mai HQ. Emerging Treatment Options for Nasopharyngeal Carcinoma. Drug Des Devel Ther. 2013;7:37-52. https://doi.org/10.2147/DDDT.S30753

Xu T, Tang J, Gu M, Liu L, Wei W, Yang H. Recurrent Nasopharyngeal Carcinoma: A Clinical Dilemma and Challenge. Curr Oncol. 2013; 20(5): e406-19. https://doi.org/10.3747/co.20.1456

Nawandar DM, Makoto Ohashi, Reza Djavadian, Elizabeth Barlow A, Kathleen Makielski, Ahmed Ali, Denis Lee, Paul F. Lambert, Eric Johannsen C, Shannon C. Kenneya C. Differentiation-Dependent LMP1 Expression Is Required for Efficient Lytic Epstein-Barr Virus Reactivation in Epithelial Cells. J Virol. 2017;91(8):1-18. https://doi.org/10.1128/JVI.02438-16

Wahyono DJ, Widikusumo A, Sulistyo H. Ekspresi Relatif mRNA LMP1 Epstein-Barr Virus dari Jaringan Tumor Terfiksasi Formalin dalam Blok Parafin sebagai Biomarker Progresivitas Tumor pada Karsinoma Nasofaring Tidak Berdiferensiasi. J Biotek Medisiana Indo. 8(1):43-50. https://doi.org/10.22435/jbmi.v8i1.2582

Mantovani F, Collavin L, Del Sal G. Mutant p53 as a guardian of the cancer cell. Cell Death Differ. 2019;26(2):199-212. https://doi.org/10.1038/s41418-018-0246-9

National Center for Biotechnology Information (US). The p53 Tumor Suppressor Protein. 1998; (Md): 346-355. https://www.ncbi.nlm.nih.gov/books/NBK22268/.

Chatterjee K, Das P, Chattopadhyay NR, Mal S, Choudhuri T. The Interplay between Epstein-Bar virus (EBV) with the p53 and Its Homologs during EBV Associated Malignancies. Heliyon. 2019; 5(11):e02624. https://doi.org/10.1016/j.heliyon.2019.e02624

Tejosukmono A, Suharto A. Hubungan Ekspresi p53 dengan Prognosis Hasil Terapi Radiasi pada Karsinoma Nasofaring Relation p53 Expression and Prognosis of Radiation Therapy in Nasopharyngeal Carcinoma. Mutiara Medika: Jurnal Kedokteran dan Kesehatan. 2012;12(3):133-137. https://doi.org/10.18196/mmjkk.v12i3.1029

Agaoglu FY, Dizdar Y, Dogan O, Alatli C, Ayan I, Savci N. P53 Overexpression in Nasopharyngeal Carcinoma. In Vivo (Brooklyn). 2004;18(5):555-560.

Fachiroh J, Schouten T, Hariwiyanto B, Paramita DK, Harijadi A, Haryana SM, & Middeldorp JM. (2004). Molecular Diversity of Epstein-Barr Virus IgG and IgA Antibody Responses in Nasopharyngeal Carcinoma: a Comparison of Indonesian, Chinese, and European Subjects. The Journal of Infectious Diseases, 53-62.

Lee AWM, Ma BBY, Ng WT, Chan ATC. Management of Nasopharyngeal Carcinoma : Current Practice and Future Management of Nasopharyngeal Carcinoma : Current Practice and Future Perspective. 2015;3356-64. https://doi.org/10.1200/JCO.2015.60.9347

Poh Y, Gan SY, Tan E. Effects of IL-6, IL-10 and TGF-β on the Expression of Survivin and Apoptosis in Nasopharyngeal Carcinoma TW01 Cells. 2012:34(2): 85-9.

Tabyaoui I, Serhier Z, Sahraoui S, Sayd S, Cadi R, Bennani OM. Immunohistochemical Expression of Latent Membrane Protein 1 ( LMP1) and p53 in Nasopharyngeal Carcinoma : Moroccan Experience. 2013;13(3):710-717. https://doi.org/10.4314/ahs.v13i3.27

Elemam IBY, Yousif M, Mohammed Y, and Elaziz SA. Immunohistochemical Expression of Latent Membrane Protein- 1 (Lmp-1) Among Sudanese Patients with Nasopharyngeal Carcinoma. Int J Res -Granthaalayah. 2015;3(9):101-107. https://doi.org/10.29121/granthaalayah.v3.i9.2015.2950

Singh P. Sample Size for Experimental Studies. J Clin Prev Cardiol. 2012;(2):88-93.

Stenmark MH, Mchugh JB, Schipper M, Walline HM, Komarck C, Feng FY, et al. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association with Poor Prognosis. Int J Radiat Oncol Biol Phys. 2014; 88(3): 580–588. https://doi.org/10.1016/j.ijrobp.2013.11.246

Dawolo AP, Utama DS, and Kasim BI. Profil Klinis Karsinoma Nasofaring di Departemen THTKL RSUP Dr. Mohammad Hoesin Palembang Tahun 2014-2015. Maj Kedokt Sriwij. 2019;49(1):1-9.

Barnes L, Eveson JW, Reichart P, and Sidransky D. World Health Organization Classification of Tumours Pathology & Genetics Head and Neck Tumours IARC WHO Classification Head and Neck Tumours.

Fatusi O, Akinpelu O, and Amusa Y. Challenges of Managing Nasopharyngeal Carcinoma in a Developing Country. J Natl Med Assoc. 2006;98(5):758-764.

Chang YL. Nasopharyngeal Carcinoma in Taiwan. J Formos Med Assoc. 1992;91 Suppl 1:362-368.

Tsao SW, Yip YL, Tsang CM, Pang PS, Lau VMY, and Lo GZKW. Etiological Factors of Nasopharyngeal Carcinoma. Oral Oncol. 2014;50(5):330-338.

Guo X, Johnson RC, Deng H, Liao J, Guan LGW, Nelson. Evaluation of Non-viral Risk Factors for Nasopharyngeal Carcinoma in a High-risk Population of Southern China. Int J Cancer. 2009;124(12):2942–2947.

Kumar V, Abul K, Abbas JCA. Robbins Pathologic Basis of Disease.; 10th Edition, 2018, Elsevier, Philadelphia, USA.

Ismail AF, dan Savitri E. Karakteristik Pasien Karsinoma Nasofaring di Rumah Sakit Umum Pusat Dr. Wahidin Sudirohusodo dan Rumah Sakit Universitas Hasanuddin Periode Tahun 2012 – 2016. Skripsi. FK Univ Hasanudin. 2017.

International Agency for Research on Cancer (IARC). Indonesia - Global Cancer Observatory. Globocan. 2020;858:1-2.

Xie SH, Yu ITS, Tse LA, Mang OWK, Yue L. Sex Difference in the Incidence of Nasopharyngeal Carcinoma in Hong Kong 1983-2008: Suggestion of a Potential Protective Role of Oestrogen. Eur J Cancer. 2013;49(1):150-155. https://doi.org/10.1016/j.ejca.2012.07.004

Sulaksana MA, and Kadriyan H. Characteristics and Risk Factors of Patients with Nasopharyngeal Carcinoma in West Nusa Tenggara Hospital. Int J Nasopharyngeal Carcinoma. 2019;1(03):83-85. https://doi.org/10.32734/ijnpc.v1i03.2058

Utama DS. The Characteristics of Adolescents Nasopharyngeal Carcinoma Patients in Mohammad Hoesin General Hospital Palembang January 2013-December 2017. 2019;01(01):2017-2019. https://doi.org/10.32734/ijnpc.v1i1.955

Licitra L, Felip E, Chan ATC, Gre V. Clinical Practice Guidelines Nasopharyngeal Cancer : EHNS – ESMO – ESTRO Clinical Clinical Practice Guidelines. 2010; 21 (Supplement 5): 187-189. https://doi.org/10.1093/annonc/mdq186

Zeng Y, Chen H, Xiang Z, Liu F, and Liu L. Case Report Nasopharyngeal Carcinoma with Metastasis to the Central Nervous System : a Report of Two Patients and Review of the Literature. 2019;12(11):4142-4149.

Brennan B. Nasopharyngeal Carcinoma. 2006;5:1-5. https://doi.org/10.1186/1750-1172-1-23

Bensouda Y, Kaikani W, Ahbeddou N, Rahhali R, Jabri M, Mrabti H. Treatment for, Metastatic Nasopharyngeal Carcinoma. Eur Ann Otorhinolaryngol Head Neck Dis. 2011;128(2):79-85. https://doi.org/10.1016/j.anorl.2010.10.003

Khabir A, Karray H, Rodriguez S, Rose M, Daoud J, Frikha M. EBV Latent Membrane Protein 1 Abundance Correlates with Patient Age but not with Metastatic Behavior in North African Nasopharyngeal Carcinomas. 7:1-7. https://doi.org/10.1186/1743-422X-2-39

Hau PM, Tsang CM, Yip YL, Huen MSY, and Tsao SW. Id1 Interacts and Stabilizes the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in Nasopharyngeal Epithelial Cells. PLoS ONE, 2011;6(6):1-10. https://doi.org/10.1371/journal.pone.0021176

Zheng H, Li L, Hu D, Deng X, and Cao Y. Role of Epstein-Barr Virus Encoded Latent Membrane Protein 1 in the Carcinogenesis of Nasopharyngeal Carcinoma. Cell Mol Immunol. 2007 Jun;4(3):185-96.

Gullo C, Low WK, and Teoh G. Association of Epstein-Barr Virus with Nasopharyngeal Carcinoma and Current Status of Development of Cancer-derived Cell Lines. Ann Acad Med Singap. 2008 Sep;37(9):769-77.

Lin C-T. Relationship between Epstein-Barr Virus Infection and Nasopharyngeal Carcinoma Pathogenesis. Chin J Cancer. 2009;28(8):1-14.

Lai-fa Sheu, Ann Chen, Hui-Hwa Tseng, Fur-Jiang Leu, John K Lin K-CHC-LM. Assessment of p53 Expression in Nasopharyngeal Carcinoma. Hum Pathol. 1995;26(4):380-386.

Agus S, Harijadi. Ekspresi p53 dan p21 waf/cip-1 pada Karsinoma Nasofaring. Maj Patol Indones. 2004;13:86-91.

Taweevisit M. Overexpression of p53 and Neoplastic Cell Proliferation in Undifferentiated Nasopharyngeal Carcinoma. Southeast Asian J Trop Med Public Heal. 2007;38(1):136-140.

Zhang P, Wu SKE, Wang Y. p53 , MDM2 , eIF4E and EGFR Expression in Nasopharyngeal Carcinoma and their Correlation with Clinicopathological Characteristics and Prognosis : A retrospective Study. 2015:113-118. https://doi.org/10.3892/ol.2014.2631

Lee BK, Linton RE, and Nissom PM. Investigating the Influence of Epstein-Barr Virus on the p53 Pathway in Nasopharyngeal Carcinoma Investigating the Influence of Epstein-Barr Virus on the p53 Pathway in Nasopharyngeal Carcinoma. 2019:0-8. https:// 10.1088/1742-6596/1175/1/012078

Gurning PPB, Nadjib MDL, and Delyuzar D. Ekspresi LMP1 pada Sel Tumor Sediaan Sitologi Biopsi Aspirasi Kelenjar Getah Bening Leher pada Metastasis Karsinoma Nasofaring. Majalah Patologi. 2015;24(2):39-46.

Sarac S, Akyol MU, Kanbur B, Poyraz A, Akyol G, Yilmaz T. Bcl-2 and LMP1 Expression in Nasopharyngeal Carcinomas. Am J Otolaryngol. 2001;22(6):377-382.

Nakanishi Y, Wakisaka N, Kondo S. Progression of Understanding for the Role of Epstein-Barr Virus and Management of Nasopharyngeal Carcinoma. Cancer Metastasis Rev. 2017;36(3):435-447. https://doi.org/10.1007/s10555-017-9693-x

Chow LWC, Khoo US, Yuen APW, and Wei WI. Expression of p53 in recurrent nodal metastasis from nasopharyngeal carcinoma (NPC). Eur J Surg Oncol. 1997;23(5):415-418. doi:10.1016/S0748-7983(97)93721-5

Aswarin R, Yusuf M, and Wiyadi MS. Association of Protein Expression p53 Mutants with Regional Lymph Gland Status on type III Carcinoma Nasofaring Patients. Indian J Otolaryngol Head Neck Surg. 2018;70(3):405-409. https://doi.org/10.1007/s12070-018-1401-9

Sawali H, Yunus MR, Ai CO, and Athar SHPP. Cutaneous metastases from nasopharyngeal carcinoma : a rare manifestation. Philipp J Otolaryngol Head Neck Surg. 2010;25(2):32-35. https://doi.org/10.3860/pjohns.v25i2.1638

Shao JY, Ernberg I, Biberfeld P, Heiden T, Zeng YX, Hu LF. Epstein-Barr Virus LMP1 Status in Relation to Apoptosis , P53 Expression and Leucocyte Infiltration in Nasopharyngeal Carcinoma. Anticancer Res.2004;2318:2309-2318.

Chou J, Lin YC, Kim J, You L, Xu ZBHDMJ. Nasopharyngeal Carcinoma—Review of the Molecular Mechanisms of Tumorigenesis. Head Neck Nasopharyngeal. 2011;30(7):946-963. https://doi.org/10.1002/hed.20833

Lubis M. Kaitan apoptosis dengan ekspresi p-53 dan BCL-2 pada karsinoma nasofaring. Maj Patol Indones. 2002;11:46-51.

Asri A. Penelitian Korelasi antara Latent Membrane Protein-1 Virus Epstein-Barr dengan P53 pada Karsinoma Nasofaring (Penelitian Lanjutan). 2012;1(1):4-6.




DOI: https://doi.org/10.18196/mmjkk.v22i1.13035

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