Introduction: Nasopharyngeal carcinoma (NPC) is a lymphoepithelial malignancy of the nasopharynx, one of the etiologies is the infection of Epstein–Barr virus in undifferentiated type of nasopharyngeal carcinoma. The Epstein-Barr virus Nucleus Antigen-1 (EBNA-1) is Epstein–Barr virus-encoded proteins as regulatory virus transcription. Epithelial Growth Factor Receptor (EGFR) consist of a single polypeptide chain of amino acid, ErbB members, tyrosine kinase receptor, a transmembrane glycoprotein encoded by gen location in the short arms of a chromosome and overexpression in epithelial tumors. EGFR plays a central role in signal transduction pathways which regulate key cellular functions in epithelial malignancies. and may also present in NPC. Objective: To investigate this relation of expression patterns of EBNA-1 and EGFR in a histological type of undifferentiated nasopharyngeal carcinoma. Method: Observational, analytical study with a cross-sectional method of 34 formalin-fixed within inclusion criteria are   EBNA-1 and positive staining of EGFR expression (30 patients) and exclusion criteria of negative staining of EGFR (4 patients). All biopsy samples work with paraffin embedded and resulted in hematoxylin-eosin undifferentiated histological types of the advanced stage in nasopharyngeal carcinoma. EBNA-1 and EGFR expression used immunohistochemistry staining. Result: EBNA-1 and EGFR expression level were detection and correlated with the advanced stadium of nasopharyngeal undifferentiated carcinoma. Conclusion: EBNA-1 is significantly related to EGFR expression in the advanced stadium of undifferentiated nasopharyngeal carcinoma. Overexpression of EGFR is mostly found in advanced  NPC but not in all ages. Male is dominated and overall age below 55 years old. Screening of EGFR with immunohistochemistry is highly considered before anti-EGFR treatment

Background: Epstein-Barr virus (EBV) infection in undifferentiated type nasopharyngealcarcinoma (NPC) will express antigenic proteins such as LMP1 and triggering a cascade ofimmunocompetent cells (CD4+ and CD8+). The ratio of CD4+/CD8 illustrates the potential eliminationof intracellular pathogens and tumor cells. Neoadjuvant chemotherapy will suppress the growth of tumorcells and immune system cells   that leads to cellular immune decline. Objective: To know the influence ofneoadjuvant chemotherapy on the expression of LMP1, the immune system and the relationship betweenthe expression of LMP1 with the ratio of CD4+/CD8++. Method: The design was one group before andafter intervention, with 10 samples of undifferentiated NPC, biopsied before and after neoadjuvant chemotherapy, and got immunohistochemical examination. We used mouse antihuman LMP1, mouse monoclonal antihuman CD4+ and antihuman CD8 antibodies. Data were analyzed with the WilcoxonSigned Ranks test, and Spearman’s Linear Regression. Result: After neoadjuvant chemotherapy, we + found statistically significant decline in LMP1 expression (p = 0.007), CD4+ (p = 0.041) and CD8   (p= 0.005). The ratio of CD4+/CD8 increase was not statistically significant (p = 0.646). The relationshipbetween the expression of LMP1 with the ratio of CD4++/CD8was very weak (r = 0.17) and no statisticallysignificant (p = 0.646). Conclusion: Neoadjuvant chemotherapy in undifferentiated type NPC causes adecrease in the expression of LMP1 and immunological status (CD4 + +, CD8 ) and increase in the ratioof CD4+/CD8+. The relationship between the expression of LMP1 with the ratio of CD4+ was veryweak and not significant. Keywords: nasopharyngeal carcinoma, expression of LMP1, CD4+, CD8++/CD8, ratio of CD4,neoadjuvant chemotherapy.+++/CD8+  Abstrak :  Latar belakang: Infeksi Epstein-Barr virus (EBV) pada karsinoma nasofaring (KNF) jenis takberdiferensiasiakanmengekspresikan protein antigen antara lain LMP1 dan memicu hadirnyasel-selimunokompeten(CD4+ dan CD8+). Rasio CD4+/CD8 menggambarkan potensi eliminasi patogen intraseldan sel tumor. Kemoterapi neoadjuvant akan menghambat pertumbuhan sel tumor dan juga menghambatpembentukan sel-sel sistem imun tubuh sehingga berefek pada penurunan imunitas seluler. Tujuan:Mengetahui pengaruh kemoterapi neoadjuvant terhadap ekspresi LMP1, sistem imun dan hubunganantara ekspresi LMP1 dengan rasio CD4+/ CD8++. Metode: Desain penelitian one group before and afterintervention, menggunakan 10 sampel biopsi KNF tak-berdiferensiasi, sebelum dan sesudah kemoterapineoadjuvant dilakukan pemeriksaan imunohistokimia. Antibodi yang digunakan ialah antibodi mouseantihuman LMP1, monoclonal mouse antihuman CD4+ dan antihuman CD8. Data penelitian dianalisisdengan Wilcoxon Signed Ranks test, Regresi Linier dan Spearman’s dengan program statistik SPSS forWindows. Hasil: Setelah kemoterapi neoadjuvant terjadi penurunan signifikan secara statistik baikekspresi LMP1 (p=0,007); CD4+ (p=0,041), maupun CD8+ (p=0,005). Rasio CD4++/CD8 meningkat tidaksignifikan secara statistik (p=0,646).   Hubungan antara ekspresi LMP1 dengan rasio CD4 sangatlemah (r = 0,17) dan tidak signifikan secara statistik (p=0,646). Kesimpulan: Kemoterapi neoadjuvantpada KNF jenis tak-berdiferensiasi menyebabkan penurunan ekspresi LMP1 dan status imunologi(CD4+,CD8+) serta peningkatan rasio CD4+/CD8++++/CD8/CD8. Hubungan antara ekspresi LMP1 dengan rasio CD4/CD8 sangat lemah dan tidak signifikan. Kata kunci: karsinoma nasofaring, ekspresi LMP1, CD4++, CD8+, rasio CD4, kemoterapineoadjuvant.