Latar belakang: Karsinoma nasofaring (KNF) adalah karsinoma sel skuamosa yang berasal dari epitel nasofaring. Salah satu etiologi KNF adalah infeksi Epstein-Barr virus (EBV). Pada biopsi jaringan KNF sering ditemukan genom EBV. Latent membran protein-1 (LMP-1) merupakan antigen dari EBV diekspresikan pada 65% KNF. Efek LMP-1 pada signaling salah satunya adalah memodulasi E-cadherin dan matrix metalloproteinase 9 (MMP-9) yang berperan pada proses metastasis. Metastasis adalah suatu proses yang kompleks dimana sel-sel kanker meninggalkan lokasi primer dan bermigrasi ke jaringan lain dalam tubuh. E-cadherin berfungsi sebagai mediator utama yang berperan terhadap adhesi sel-sel pada jaringan epitel, sedangkan MMP-9 menyebabkan rusaknya integritas dari matriks ekstraseluler yang merupakan barrier, sehingga memungkinkan sel tumor menginvasi jaringan sekitarnya. Tujuan: Untuk mengetahui korelasi ekspresi LMP-1 dengan ekspresi E-cadherin dan MMP-9 pada penderita KNF WHO tipe 3. Metode: Penelitian observasional analitik dengan desain potong lintang yang melibatkan 11 penderita KNF WHO tipe 3. Pemeriksaan ekspresi LMP-1, MMP-9, dan E-cadherin menggunakan metode pewarnaan imunohistokimia, dan hasilnya dihitung dengan menggunakan software ImmunoRatio. Hasil: Analisis statistik ekspresi LMP-1 dan E-cadherin menunjukkan korelasi negatif yang signifikan (p=0,000) dengan koefisien korelasi r= -0,940 (terdapat korelasi yang sangat kuat). Analisis korelasi ekspresi LMP-1 dan MMP-9 menunjukkan korelasi positif yang signifikan (p=0,000) dengan koefisien korelasi r=0,881 (terdapat korelasi yang sangat kuat). Kesimpulan: Semakin tinggi ekspresi LMP-1, maka ekspresi E-cadherin pada jaringan nasofaring penderita KNF WHO tipe 3 semakin menurun. Semakin tinggi ekspresi LMP-1 maka ekspresi MMP-9 pada jaringan nasofaring penderita KNF WHO tipe 3 semakin meningkat. Background: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma derived from nasopharynx epithel cells. Epstein-Barr virus (EBV) is one of the risk factor of NPC. EBV can often be found in NPC tissue biopsy. Latent membran protein 1 (LMP-1) is an antigen from EBV which is expressed in 65% of NPC. The effect of LMP-1 includes modifying E-cadherin and matrix metalloproteinase 9 (MMP-9) which important in metastasis. Metastasis is a complex series of steps in which cancer cells leave the original tumor site and migrate to other tissues. E-cadherin is a main mediator in adhesion between cells. Decreased of E-cadherin makes tumor cells tend to migrate to other tissues of the body. MMP-9 involved in degradation of collagen IV in basement membranes and extracellular matrix facilitating invasion, metastasis, growth, and angiogenesis. Purpose: To determine the correlation between LMP-1 with E-cadherin and MMP-9 in WHO type 3 nasopharygeal carcinoma. Method: Observational analytic study with cross sectional design involving 11 NPC patients. The expression of LMP-1, E-cadherin, and MMP-9 using immunohistochemistry staining, and the results were calculated with ImmunoRatio software. Result: Statistical analysis showed significant negative correlation between LMP-1 dan E-cadherin (p=0.000) with r= -0.940 (very strong correlation). Statistical analysis showed significant positive correlation between LMP-1 dan MMP-9 (p=0.000) with r= 0.881 (very strong correlation). Conclusion: There was a significant negative correlation between LMP-1 dan E-cadherin in tissue from type 3 NPC patient. There was a significant positive correlation between LMP-1 dan MMP- 9 in tissue from type 3 NPC patient.

BACKGROUND: Progression of laryngeal carcinoma can be classified with the clinical staging, however there are different patterns of progressions observed in the patient with the same clinical stage which also affects their prognoses. Therefore biomarkers should be used. Nuclear factor (NF)-ĸB, Cyclin-D1, vascular endothelial growth factor (VEGF), cyclooxygenase (Cox)-2 have been reported for laryngeal carcinoma. However, it is still unclear how these markers are expressed and correlated in advanced stage laryngeal carcinoma. Therefore current study was conducted to investigate the expressions of NF-ĸB, Cyclin-D1, VEGF and Cox-2 and their correlations in advanced stage laryngeal carcinoma.METHODS: Subjects were recruited and laryngeal biopsies were collected, fixed in formalin and prepared for immunohistochemistry. The immunohistochemistry was performed using mouse monoclonal anti-NF-kB p65, anti-Cyclin-D12 anti-VEGF, and anti-Cox-2 antibodies. The immunohistochemistry results were documented and measured using ImmunoRatio. Pearson or Spearman correlation test was used based on the results of Shapiro-Wilk test of normality. A p-value of less than 0.05 is considered statistically significant.RESULTS: Twelve male subjects were included in this study. Expressions of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 were clearly observed. Mean of NF-ĸB, Cyclin-D1, VEGF dan Cox-2 IHC expression levels measured with ImmunoRatio were 57.50±20.06%, 45.00±24.31%, 43.33±17.23% and 40.42±16.98%, respectively. There was significant correlation between the expressions of VEGF dan Cox-2 (p=0.031, r=0.622).CONCLUSION: Since correlation between the VEGF and Cox-2 expressions was statistically significant, VEGF and Cox-2 might have important roles in the growth, invasion and metastasis of laryngeal carcinoma.KEYWORDS: advanced stage laryngeal carcinoma, immunohistochemistry, NF-ĸB, Cyclin-D1, VEGF, Cox-2

Latar Belakang: Karsinoma nasofaring (KNF) merupakan keganasan tersering pada kepala dan leher. Pilihan terapi KNF adalah radioterapi dan kemoterapi yang berhubungan dengan toksisitas, resistensi obat, dan rekurensi. Intervensi metabolik yang didasarkan pada perubahan metabolisme sel kanker merupakan salah satu strategi terapi kanker pada saat ini. Untuk dapat mengetahuinya perlu dipahami pengaruh ekspresi p53 dan hypoxia-inducible factor 1 (HIF1) terhadap peningkatan kadar laktat jaringan nasofaring pada pasien KNF. Tujuan: Mengetahui pengaruh ekspresi p53 dan HIF1 terhadap peningkatan kadar laktat jaringan nasofaring, dan untuk mengetahui kesesuaian antara kadar laktat darah dengan laktat jaringan nasofaring. Metode: Penelitian cross sectional melibatkan 10 subjek, dilakukan biopsi nasofaring dengan tuntunan nasoendoskopi untuk pemeriksaan histopatologi, ekspresi p53 dan HIF1 dengan imunohistokimia, laktat jaringan nasofaring dengan colorimetric, dan laktat darah. Hasil: Seluruh subjek mengalami peningkatan ekspresi p53 dan HIF1 dengan rerata p53 19,53±7,37 dan HIF1 24,30±12,28. Seluruh subjek penelitian memiliki kadar laktat jaringan meningkat, dengan rerata kadar laktat 0,67±0,39. Kadar laktat darah subjek cenderung meningkat dengan rerata 2,93±0,65. Terdapat pengaruh peningkatan ekspresi p53 terhadap peningkatan kadar laktat jaringan (p=0,002). Terdapat pengaruh peningkatan ekspresi HIF1 terhadap peningkatan kadar laktat jaringan (p=0,042). Tidak terdapat kesesuaian antara kadar laktat darah dengan laktat jaringan nasofaring (p=0,000). Kesimpulan: Peningkatan ekspresi p53 dan HIF1 berpengaruh terhadap peningkatan kadar laktat jaringan nasofaring pada pasien KNF, namun kadar laktat darah tidak menggambarkan kadar laktat jaringan nasofaring. ABSTRACTBackground: Nasopharyngeal carcinoma (NPC) is the most frequent malignancy of the head and neck. The options of NPC therapy are radiotherapy and chemotherapy, associated with toxicity, drug resistance, and recurrence. Metabolic intervention based on changes in cancer cell metabolism is currently one of the strategies of cancer therapy. Aim: To determine the impact of p53 and hypoxia-inducible factor 1 (HIF1) expression on elevated lactate levels of nasopharyngeal tissue, and to determine the compatibility between blood lactate and nasopharyngeal tissue lactate levels in patients with NPC. Method: This cross-sectional study involved 10 subjects who underwent nasopharyngeal biopsy for histopathologic examination, p53 and HIF1 expression using immunohistochemistry, lactate of nasopharyngeal tissue using colorimetric, and blood lactate. Results: All subjects had increased expression of p53 and HIF1 with p53 mean of 19.53±7.37 and HIF1 mean of 24.30±12.28. All subjects had elevated tissue lactate levels, with lactate levels mean of 0.67±0.39. The blood lactate level of the subjects increased, with blood lactate level mean of 2.93±0.65. There was a significant increasing impact of p53 expression on tissue lactate elevated level (p=0.002) and a significant increasing impact of HIF1 expression on tissue lactate elevated level (p=0.042). There was no correlation between lactate levels of blood lactate and nasopharyngeal tissue (p=0.000). Conclusion: Increased expression of p53 and HIF1 had an effect on increased levels of lactate nasopharyngeal tissue in NPC patients, but blood lactate levels did not have a correlation with lactate levels of nasopharyngeal tissue.

Latar Belakang: Karsinoma nasofaring (KNF) merupakan keganasan yang tersering ditemukan, dan berdampak pada penurunan kualitas hidup serta memiliki mortalitas tinggi. Penanganan KNF selama ini terkendala oleh waktu tunggu yang cukup lama dalam menentukan staging KNF terutama untuk antrian pemeriksaan computed tomography scan (CT scan) dan Ultrasonography (USG). Pemeriksaan kadar DNA EBV (Deoxyribonucleic acid Epstein-Barr Virus) pada pasien yang relatif lebih mudah dan terjangkau dapat digunakan untuk memprediksi stadium dan prognosis KNF. Dengan mengetahui prognosis KNF lebih dini, maka diharapkan penanganan terhadap KNF dapat segera dilakukan. Tujuan: Mengetahui apakah kadar DNA EBV dapat dipakai untuk memprediksi stadium dan prognosis KNF dengan cara mencari hubungan antara kadar DNA EBV dengan stadium KNF. Metode: Penelitian cross sectional melibatkan 15 subjek penelitian yang terdiagnosis KNF WHO tipe 3 kemudian dilakukan staging dengan CT scan, USG abdomen, dan foto toraks, serta diambil sampel darah untuk diukur kadar DNA EBV. Hasil: Seluruh subjek penelitian mengalami peningkatan kadar DNA EBV sesuai dengan peningkatan stadium KNF. Peningkatan stadium KNF berhubungan signifikan dengan peningkatan kadar DNA EBV (p=0,001). Ukuran tumor (T) berhubungan signifikan dengan kadar DNA EBV (p=0,023), ukuran nodul (N) berhubungan signifikan dengan kadar DNA EBV (p=0,005), ada tidaknya metastasis tidak berhubungan signifikan dengan kadar DNA EBV (p=0,398). Nilai cut off kadar DNA EBV sebesar 952 kopi/ml. Kesimpulan: Terdapat hubungan yang signifikan antara kadar DNA EBV dengan stadium klinis, dengan demikian kadar DNA EBV dapat dipertimbangkan untuk digunakan sebagai prediktor stadium dan prognosis KNF. Background: Nasopharyngeal carcinoma (NPC) is the predominant tumor type arising in the nasopharynx,  with a high mortality and affecting quality of life.  NPC treatment  management is hindered by long queues of Computed Tomography Scan (CT scan) and Ultrasonography (USG) examinations to ascertain the NPC staging. The examination of Epstein-Barr Virus (EBV) DNA level is relatively simpler and inexpensive  to predict the NPC staging and prognosis, thus, it can speed up NPC treatment. Objective: To determine whether EBV DNA level can be used to predict the NPC  stage and prognosis by finding a correlation between EBV DNA level and NPC stage. Method: This was  a cross-sectional study involving 15 respondents who were diagnosed as WHO type 3 NPC, and examined by CT scan, abdominal ultrasound, chest X-ray,  and blood  test for measuring the levels of EBV DNA to determine the stage. Results: All respondents had elevated levels of EBV DNA in accordance with NPC stage elevation. Increased NPC stages were significantly correlated with elevated levels of EBV DNA (p=0.001). The size of tumor (T) was significantly correlated with EBV DNA (p=0.023), the size of nodule (N) was significantly correlated with EBV DNA (p=0.005).  The presence or absence of metastasis did not significantly correlate with EBV DNA (p=0.398). The EBV DNA cut off value was 952 copies/ml. Conclusions: There  was a significant correlation between EBV DNA levels and clinical stages, hence EBV DNA can be considered to be used as NPC staging and prognosis predictor.