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Pengaruh ekspresi p53 dan HIF1 terhadap peningkatan laktat jaringan nasofaring pada pasien karsinoma nasofaring Kurniawan, Jemmy; Rahaju, Pudji; Soehartono, Soehartono
Oto Rhino Laryngologica Indonesiana Vol 48, No 1 (2018): Volume 48, No. 1 January - June 2018
Publisher : PERHATI-KL

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.

Correlation of LMP-1 expression with KRAS and Cyclin-D1 expressions in WHO type III NPC patients Neri, Rizki Amelia Yurika; Soehartono, Soehartono; Surjotomo, Hendradi
Oto Rhino Laryngologica Indonesiana Vol. 54 No. 1 (2024): VOLUME 54, NO. 1 JANUARY - JUNE 2024
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32637/orli.v54i1.493

Background: Nasopharyngeal carcinoma (NPC) is a malignancy with pathologically andepidemiologically unique characteristics. The risk factors that are often associated with NPC are chronicEBV infection, environmental factors, and epigenetic changes. EBV infection expresses Latent MembraneProtein-1 (LMP-1) in NPC. The role of LMP-1 is to activate signaling pathways, including KRAS-RAFMEK-ERK which induces transcription of cyclin D1 that contributes to cell proliferation. Purpose: Todetermine the correlation between LMP-1 expression and KRAS expression, LMP-1 expression with cyclinD1 expression, and KRAS expression with cyclin D1 expression in nasopharyngeal tissue of WHO typeIII NPC patients. Method: Analytical observational study with a cross-sectional approach involving 30paraffin blocks of biopsy tissue from NPC patients who had not received radiotherapy or chemotherapy.Expression of LMP-1, KRAS, and cyclin D1 was examined with immunohistochemical staining methodand calculated using manual counting by anatomical pathologists. Result: Statistical analysis of LMP-1expression with KRAS expression showed an insignificant positive correlation (p=0.546) with a correlationcoefficient (ρ=0.115). The LMP-1 expression with cyclin D1 expression showed an insignificant positivecorrelation (p=0.305) with a correlation coefficient (ρ=0.194). The KRAS expression with cyclin D1expression showed an insignificant positive correlation (p=0.262) with a correlation coefficient (ρ=0.212). Conclusion: In WHO type III NPC tissue in the proliferative process, an increase in LMP-1 expression(53.4%±27.35%,) was followed by an increase in KARS expression (49.83%±22.83%) and D1 expression(42.27%±31.94%) as well as an increase in KRAS expression (42.27%±31.94%) followed by an increasein cyclin D1 expression (42.27%±31.94%) although not significant.

Correlation of LMP-1 expression with KRAS and IL-8 expression in NPC WHO type III Soehartono, Soehartono; Marini, Marini; Surjotomo, Hendradi; Fadli, Muhammad Luqman; Setijowati, Nanik
Oto Rhino Laryngologica Indonesiana Vol. 54 No. 2 (2024): VOLUME 54, NO. 2 JULY - DECEMBER 2024
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32637/orli.v54i2.530

Background: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma originating from mucosal epithelium of the nasopharynx with complex disease progression. About 95% are caused by Epstein-Barr virus (EBV) infection which is characterized by the detection of viral gene product protein of Latent Membrane Protein-1 (LMP-1). Tumor growth and metastasis depend on the mechanism of angiogenesis. Interleukin-8 (IL-8) is a potent angiogenic factor and involved in the angiogenesis mechanism. Kirsten Rat Sarcoma (KRAS) is one of the proto-oncogenes that has an increased expression of more than 60% in NPC. The KRAS activation played a role in the modulation of IL-8 expression by triggering several important signaling pathways, which triggered neovascularization in the process of angiogenesis. Purpose: To determine the correlation between expression of LMP-1 with KRAS and IL-8, in mechanism of angiogenesis in NPC WHO type III. Method: Analytical observational study with a cross-sectional approach involving 30 paraffin blocks of biopsy tissue from NPC patients who had not received radiotherapy or chemotherapy. Expressions of LMP-1, KRAS, and IL-8 were examined with immunohistochemistry (IHC) staining method, and calculated using manual counting by Anatomic Pathologists. Result: Statistical analysis of LMP-1 expression with KRAS showed an insignificant positive correlation (p=0.546), with a correlation coefficient (ρ=0.115). The KRAS expression with IL-8 showed an insignificant positive correlation (p=0.851), with a correlation coefficient (ρ=0.036). The LMP-1 expression with IL-8 showed a significant positive correlation (p=0.042), with a correlation coefficient (ρ=0.321). Conclusion: The increase in the expression of LMP-1 was followed with the increase in the IL-8 expression. Keywords: NPC, LMP-1, KRAS, IL-8, angiogenesis ABSTRAK Latar belakang: Karsinoma nasofaring (KNF) adalah karsinoma sel skuamosa yang berasal dari epitel mukosa nasofaring. Perkembangannya melibatkan hubungan yang kompleks. Sekitar 95% disebabkan oleh infeksi virus Epstein-Barr (VEB) yang ditandai dengan terdeteksinya protein produk gen virus, salah satunya yaitu Latent Membrane Protein-1 (LMP-1). Pertumbuhan dan metastasis tumor tergantung pada mekanisme angiogenesis. Interleukin-8 (IL-8) adalah faktor angiogenik yang kuat, dan terlibat dalam mekanisme angiogenesis. Kirsten Rat Sarcoma (KRAS) merupakan salah satu proto- onkogen yang mengalami peningkatan ekspresi lebih dari 60% pada KNF. Aktivasi KRAS memainkan peran dalam modulasi ekspresi IL-8 dengan memicu beberapa jalur sinyal penting, dan hal ini dapat memicu neovaskularisasi pada proses angiogenesis. Tujuan: Mengetahui korelasi antara ekspresi LMP-1 dengan ekspresi KRAS dan IL-8 dalam mekanisme angiogenesis KNF WHO tipe III. Metode: Penelitian observasional analitik dengan pendekatan potong lintang yang melibatkan 30 blok parafin jaringan biopsi penderita KNF yang belum mendapat pengobatan radioterapi maupun kemoterapi. Pemeriksaan ekspresi LMP-1, KRAS, dan IL-8 menggunakan pewarnaan imunohistokimia, dan hasilnya dihitung secara manual oleh ahli Patologi Anatomi. Hasil: Analisis statistik ekspresi LMP-1 dengan KRAS menunjukkan korelasi positif yang tidak signifikan (p =0,546), dengan koefisien korelasi ρ=0,115. Ekspresi KRAS dengan IL-8 menunjukkan korelasi positif yang tidak signifikan (p=0,851), dengan koefisien korelasi ρ=0,036. Ekspresi LMP-1 dengan IL-8 menunjukkan korelasi positif yang signifikan (p=0,042), dengan koefisien korelasi ρ=0,321. Kesimpulan: Semakin tinggi ekspresi LMP-1, maka diikuti oleh tingginya ekspresi IL-8. Kata kunci: KNF, LMP-1, KRAS, IL-8, angiogenesis

Correlation of LMP-1 expression with KRAS and IL-8 expression in NPC WHO type III Soehartono, Soehartono; Marini, Marini; Surjotomo, Hendradi; Fadli, Muhammad Luqman; Setijowati, Nanik
Oto Rhino Laryngologica Indonesiana Vol. 54 No. 2 (2024): VOLUME 54, NO. 2 JULY - DECEMBER 2024
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32637/orli.v54i2.530

Background: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma originating from mucosal epithelium of the nasopharynx with complex disease progression. About 95% are caused by Epstein-Barr virus (EBV) infection which is characterized by the detection of viral gene product protein of Latent Membrane Protein-1 (LMP-1). Tumor growth and metastasis depend on the mechanism of angiogenesis. Interleukin-8 (IL-8) is a potent angiogenic factor and involved in the angiogenesis mechanism. Kirsten Rat Sarcoma (KRAS) is one of the proto-oncogenes that has an increased expression of more than 60% in NPC. The KRAS activation played a role in the modulation of IL-8 expression by triggering several important signaling pathways, which triggered neovascularization in the process of angiogenesis. Purpose: To determine the correlation between expression of LMP-1 with KRAS and IL-8, in mechanism of angiogenesis in NPC WHO type III. Method: Analytical observational study with a cross-sectional approach involving 30 paraffin blocks of biopsy tissue from NPC patients who had not received radiotherapy or chemotherapy. Expressions of LMP-1, KRAS, and IL-8 were examined with immunohistochemistry (IHC) staining method, and calculated using manual counting by Anatomic Pathologists. Result: Statistical analysis of LMP-1 expression with KRAS showed an insignificant positive correlation (p=0.546), with a correlation coefficient (ρ=0.115). The KRAS expression with IL-8 showed an insignificant positive correlation (p=0.851), with a correlation coefficient (ρ=0.036). The LMP-1 expression with IL-8 showed a significant positive correlation (p=0.042), with a correlation coefficient (ρ=0.321). Conclusion: The increase in the expression of LMP-1 was followed with the increase in the IL-8 expression. Keywords: NPC, LMP-1, KRAS, IL-8, angiogenesis ABSTRAK Latar belakang: Karsinoma nasofaring (KNF) adalah karsinoma sel skuamosa yang berasal dari epitel mukosa nasofaring. Perkembangannya melibatkan hubungan yang kompleks. Sekitar 95% disebabkan oleh infeksi virus Epstein-Barr (VEB) yang ditandai dengan terdeteksinya protein produk gen virus, salah satunya yaitu Latent Membrane Protein-1 (LMP-1). Pertumbuhan dan metastasis tumor tergantung pada mekanisme angiogenesis. Interleukin-8 (IL-8) adalah faktor angiogenik yang kuat, dan terlibat dalam mekanisme angiogenesis. Kirsten Rat Sarcoma (KRAS) merupakan salah satu proto- onkogen yang mengalami peningkatan ekspresi lebih dari 60% pada KNF. Aktivasi KRAS memainkan peran dalam modulasi ekspresi IL-8 dengan memicu beberapa jalur sinyal penting, dan hal ini dapat memicu neovaskularisasi pada proses angiogenesis. Tujuan: Mengetahui korelasi antara ekspresi LMP-1 dengan ekspresi KRAS dan IL-8 dalam mekanisme angiogenesis KNF WHO tipe III. Metode: Penelitian observasional analitik dengan pendekatan potong lintang yang melibatkan 30 blok parafin jaringan biopsi penderita KNF yang belum mendapat pengobatan radioterapi maupun kemoterapi. Pemeriksaan ekspresi LMP-1, KRAS, dan IL-8 menggunakan pewarnaan imunohistokimia, dan hasilnya dihitung secara manual oleh ahli Patologi Anatomi. Hasil: Analisis statistik ekspresi LMP-1 dengan KRAS menunjukkan korelasi positif yang tidak signifikan (p =0,546), dengan koefisien korelasi ρ=0,115. Ekspresi KRAS dengan IL-8 menunjukkan korelasi positif yang tidak signifikan (p=0,851), dengan koefisien korelasi ρ=0,036. Ekspresi LMP-1 dengan IL-8 menunjukkan korelasi positif yang signifikan (p=0,042), dengan koefisien korelasi ρ=0,321. Kesimpulan: Semakin tinggi ekspresi LMP-1, maka diikuti oleh tingginya ekspresi IL-8. Kata kunci: KNF, LMP-1, KRAS, IL-8, angiogenesis

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