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A Pilot Study on Immunohistochemical Expressions of NF-ĸB, Cyclin-D1, VEGF, and Cox-2 in Advanced Stage Laryngeal Carcinoma Pudji Rahaju; Ayunita Tri Wirattami; Ferry Sandra; Steffi Kurniawan; Khairun Nisa; Soehartono Soehartono; Edi Handoko; Ahmad Dian Wahyudiono; Hendradi Surjotomo; Hendy Setyo Yudhanto; Nanik Setjowati
The Indonesian Biomedical Journal Vol 13, No 4 (2021)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v13i4.1580

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

Korelasi ekspresi LMP-1 dengan ekspresi E-chaderin dan MMP-9 pada mekanisme metastasis penderita KNF WHO tipe 3 Adrian Benediktus; Soehartono Soehartono; Hendradi Surjotomo
Oto Rhino Laryngologica Indonesiana Vol 49, No 1 (2019): Volume 49, No. 1 January-June 2019
Publisher : PERHATI-KL

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.

Correlation of nodule with body mass index and Karnofsky status in nasopharyngeal carcinoma chemotherapy Bagus Harning Efranto; Soehartono -; Edi Handoko
Oto Rhino Laryngologica Indonesiana Vol 51, No 1 (2021): Volume 51, No. 1 January - June 2021
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32637/orli.v51i1.412

Background: Nasopharyngeal carcinoma (NPC) is a malignancy arising from the nasopharyngeal epithelium, usually present in the Rosenmüller fossa. NPC is a cancer of the head and neck that is most common in Indonesia. The main therapeutic for NPC is radiotherapy. Neoadjuvant chemotherapy reduces the local spread of advanced NPC, optimizing the eradication of micrometastases, and improved local control. Neoadjuvant chemotherapy’s effectiveness can be assessed by changes in the patient’s neck nodule size (N), Body Mass Index (BMI), and Karnofsky’s status. Purpose: To determine the correlation between N with BMI and Karnofsky status on neoadjuvant chemotherapy with Cisplatin and 5-Fu in WHO type 3 of NPC patients. Method: Analytical observational study using medical record data. An assessment of N, BMI and Karnofsky status of NPC WHO type 3 of 23 patients who had undergone neoadjuvant chemotherapy using Cisplatin and 5-Fu for three cycles. Result: The N value decreased, p = 0.001. BMI value decreased, p = 0.615. Karnofsky’s status value, p = 0.564. The correlation between N and BMI before and after three cycles of neoadjuvant chemotherapy: r = -0.201 and p = 0.358 ; r = -0.070 and p = 0.751. Correlation of N with Karnofsky status: r = 0.155 and p = 0.480; r = 0.571 and p = 0.004. Conclusion: Neoadjuvant chemotherapy with Cisplatin and 5-Fu was effective towards reducing the N and also in correlation between N and BMI but less effective in the correlation between N and Karnofsky status.ABSTRAK Latar belakang: Karsinoma nasofaring (KNF) adalah keganasan yang berasal dari epitel nasofaring yang biasanya timbul di fossa Rosenmüller. KNF merupakan kanker di kepala dan leher yang paling umum terjadi di Indonesia. Terapi utama pada KNF adalah radioterapi. Kemoterapi neoajuvan dapat menurunkan penyebaran lokal KNF stadium lanjut, mengoptimalkan eradikasi mikrometastasis, dan meningkatkan kontrol lokal. Efektivitas kemoterapi neoajuvan dapat dinilai dengan perubahan ukuran nodul leher (N) pasien, indeks massa tubuh (IMT) dan status Karnofsky pasien. Tujuan: Mengetahui korelasi antara N dengan IMT dan status Karnofsky pada pemberian kemoterapi neoajuvan Cisplatin dan 5-Fu pada pasien KNF WHO tipe 3. Metode: Penelitian observasional analitik dengan menggunakan data rekam medis. Penilaian dilakukan terhadap N, IMT dan status Karnofsky pada 23 pasien KNF WHO tipe 3 yang telah menjalani kemoterapi neoajuvan dengan menggunakan Cisplatin dan 5-Fu sebanyak tiga siklus. Hasil: Nilai N menurun, p=0,001. Nilai IMT menurun, p=0,615. Nilai status Karnofsky, p=0,564. Korelasi antara N dengan IMT sebelum dan setelah tiga siklus kemoterapi neoajuvan: r= -0,201 dan p= 0,358; r= -0,070 dan p=0,751. Korelasi N dengan status Karnofsky: r=0,155 dan p=0,480; r=0,571 dan p=0,004. Kesimpulan: Kemoterapi neoajuvan dengan Cisplatin dan 5-Fu efektif terhadap penurunan N serta korelasi antara N dengan IMT, namun kurang efektif menilai korelasi antara N dengan Status Karnofsky.Kata kunci: karsinoma nasofaring, kemoterapi neoajuvan,nodul, indeks massa tubuh, status Karnofsky

Korelasi ekspresi IL-6 dengan STAT3 pada metastasis penderita KNF WHO tipe 3 LMP-1 positif S. Soehartono; Monika Teresa Prasetyo; Hendradi Surjotomo; Hendy Setyo Yudhanto
Oto Rhino Laryngologica Indonesiana Vol 49 (2019): Volume 49, No. 2 July - December 2019
Publisher : PERHATI-KL

Latar belakang: Karsinogenesis karsinoma nasofaring sangat kompleks, dan disebabkan oleh interaksi antara infeksi kronis Epstein-Barr Virus (EBV), faktor lingkungan, dan perubahan genetik serta epigenetik. Latent Membrane Protein (LMP)-1 merupakan antigen utama EBV. LMP-1 diyakini menstimulasi ekspresi sitokin yang memengaruhi perilaku sel epitel, salah satunya adalah Interleukin (IL)- 6. IL-6 akan mengaktivasi jalur Signal Transducer and Activator of Transcription (STAT)3. Peningkatan ekspresi IL-6 dan STAT3 memiliki kaitan erat dalam lingkungan mikro tumor KNF, namun peran IL-6 dan STAT3 dalam modulasi migrasi dan invasi sel KNF masih belum jelas diketahui. Tujuan: Mengetahui korelasi antara ekspresi IL-6 dan ekspresi STAT3 di jaringan nasofaring dengan metastasis penderita KNF WHO tipe III LMP-1 positif. Metode: Penelitian observasional analitik dengan pendekatan cross-sectional yang melibatkan 15 penderita KNF WHO tipe III LMP-1 positif. Pemeriksaan ekspresi LMP-1, IL-6, dan STAT3 menggunakan metode pewarnaan imunohistokimia, dan hasilnya dihitung dengan menggunakan software ImmunoRatio. Penentuan stadium klinis metastasis berdasarkan pemeriksaan klinis dan penunjang radiologis, kemudian dievaluasi nilai TNM menggunakan AJCC 2017. Hasil: Analisis statistik ekspresi IL-6 dan STAT3 menunjukkan korelasi yang signifikan (p=0,020) dengan koefisien korelasi r=0,592. Tidak terdapat perbedaan ekspresi IL-6 yang bermakna di antara penderita stadium III, IVa, dan IVb (p=0,116). Terdapat perbedaan ekspresi STAT3 yang signifikan di antara penderita dengan stadium III, IVa, dan IVb (p=0,038). Kesimpulan: Semakin tinggi ekspresi IL-6 maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif semakin meningkat. Semakin tinggi stadium klinis, maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif akan meningkat. Kata kunci: karsinoma nasofaring, Virus Epstein-Barr, LMP-1, IL-6, STAT3 ABSTRACT Background:Carcinogenesis of NPC is complex interactions among chronic EBV infection, environmental factors, genetic and epigenetic. LMP-1 is EBV’s antigen most expressed in NPC cases. LMP-1 is believed to stimulate expression of cytokines that affect the behavior of epithelial cells, i.e. Interleukin-6 (IL-6) which will activate the STAT3 pathway. Increased expression of IL-6 and STAT3 has a close relationship in tumor microenvironment of NPC patients, but the role of IL-6 and STAT3 themselves in modulation of migration and invasion of NPC cells are not yet fully understood. Purpose: To find out the correlation between IL-6 expression and STAT3 expression in the nasopharyngeal tissue of NPC patients with LMP-1 positive metastatic WHO type III. Method: Observational analytic study with cross-sectional approach involving 15 patients WHO type III LMP-1 positive NPC patients. Examination of LMP-1, IL-6, and STAT3 using immunohistochemical, and the results were calculated using ImmunoRatio. Clinical staging of metastases based on clinical examination and radiological imaging then synchronized with AJCC 2017. Result: Expressions of IL-6 and STAT3 showed significant correlation (p=0.020) with coefficient r=0.592. There were no differences in IL-6 expression among patients with stage III, IVa, and IVb (p=0.116). There were significant differences in STAT3 expression among patients with stage III, IVa, and IVb (p=0.038). Conclusion: There was a significant positive correlation between IL-6 and STAT3 in tissue from WHO type III LMP-1 positive NPC patients. The higher the clinical stage, the expression of STAT3 in the nasopharyngeal tissue of positive WHO type III LMP-1 NPC patients will increase.

Hubungan Antara Kadar DNA Plasma Virus Epstein Barr Dengan Stadium Klinis Karsinoma Nasofaring WHO Tipe 3 Putranti Dyahayu Roziaty; Soehartono soehartono; Hendradi Surjotomo
Oto Rhino Laryngologica Indonesiana Vol 48, No 2 (2018): Volume 48, No. 2 July - December 2018
Publisher : PERHATI-KL

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.

The effect of neutrophil-lymphocyte ratio on neck nodule size in nasopharyngeal carcinoma chemotherapy Soehartono -; Dwi Novitasari; Iriana Maharani
Oto Rhino Laryngologica Indonesiana Vol 52, No 2 (2022): VOLUME 52, NO. 2 JULY - DECEMBER 2022
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar

ABSTRACTBackground: Nasopharyngeal carcinoma (NPC) is a cancer of the head and neck, that ranks as the 4th most malignant cancer in Indonesia. The prognosis of NPC patients is determined from the clinical stage based on the Tumor, Nodule, Metastatic (TNM) classification system. These prognosis factors are not entirely reliable for predicting treatment outcomes. The Neutrophil Lymphocyte Ratio (NLR) represents an index of pro-tumor and anti-tumor activity, that can be used to predict the outcome of neoadjuvant chemotherapy and the patient’s well-being as assessed by Karnofsky status, Body Mass Index (BMI), and neck nodule size (NNS). Purpose: To study the effect of NLR on Karnofsky status, BMI, and NNS in WHO type III NPC patients who underwent 3 cycles of neoadjuvant chemotherapy. Method: Analytical observational research with a cohort-retrospective approach on WHO type III NPC subjects who underwent platinum-based regimen neoadjuvant chemotherapy. NLR pre-chemotherapy was analyzed for its effect on Karnofsky status, BMI, and NNS. Result: NLR had no significant effect on Karnofsky status pre- and post-chemotherapy, BMI pre- and post-chemotherapy, NNS pre-chemotherapy, changes in Karnofsky status and BMI pre-and post-chemotherapy, but had significant effect on the size of neck nodules post-chemotherapy, and changes in the size of neck nodules. Conclusion: NLR has no significant effect on Karnofsky status, on BMI pre- and post-chemotherapy, and neck nodule size pre-chemotherapy. However, NLR had a significant effect on neck nodule size post-chemotherapy and neck nodule size changes. ABSTRAKLatar belakang: Karsinoma Nasofaring (KNF) merupakan keganasan dalam bidang THT yang menempati urutan ke-4 keganasan di Indonesia. Prognosis pasien KNF terutama ditentukan dari stadium klinis berdasarkan sistem klasifikasi Tumor, Nodul, Metastasis (TNM) yang tidak sepenuhnya dapat diandalkan untuk memprediksi hasil pengobatan. Sedangkan Ratio Netrofil-Limfosit (RNL) mempresentasikan indeks aktivitas protumor dan antitumor sehingga dapat digunakan sebagai pelengkap stadium klinis untuk memprediksi hasil kemoterapi neoadjuvan dan kesejahteraan subjek melalui status Karnofsky, Index Massa Tubuh (IMT) dan ukuran nodul leher. Tujuan: Mempelajari efek Rasio Netrofil-Limfosit (RNL), Index Massa Tubuh (IMT), dan ukuran nodul leher pada subjek dengan KNF WHO tipe III yang telah menjalani 3 siklus kemoterapi neoadjuvan. Metode: Penelitian observasional analitik dengan pendekatan kohort-retrospektif menggunakan data rekam medis penderita KNF tipe III WHO yang menjalani kemoterapi neoadjuvan menggunakan regimen berbasis platinum. RNL sebelum kemoterapi dianalisis pengaruhnya terhadap status Karnofsky, IMT dan ukuran nodul leher. Hasil: RNL berpengaruh tidak signifikan terhadap status Karnofsky sebelum dan sesudah kemoterapi, IMT sebelum dan sesudah kemoterapi, ukuran nodul leher sebelum kemoterapi, perubahan status Karnofsky, perubahan IMT, namun berpengaruh signifikan terhadap ukuran nodul leher sesudah kemoterapi dan perubahan ukuran nodul leher. Kesimpulan: RNL berpengaruh tidak signifikan terhadap status Karnofsky, IMT sebelum dan sesudah kemoterapi, ukuran nodul leher sebelum kemoterapi, namun berpengaruh signifikan terhadap ukuran nodul leher sesudah kemoterapi dan perubahan ukuran nodul leher sebelum kemoterapi, namun berpengaruh signifikan terhadap ukuran nodul leher sesudah kemoterapi dan perubahan ukuran nodul leher.

Exploring The Tasting System and Clinical Significance of Taste Disorders: A Narrative Review: Clinical Significance of Taste Disorder Giovani Indah Giantoro Putri; Soehartono; Yunisa Astiarani
Journal of Urban Health Research Vol. 1 No. 3 (2023): Journal of Urban Health Research
Publisher : School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25170/juhr.v1i3.4476

Introduction: This review took an in-depth look at the intricate anatomy of taste buds, unveiling their complex structure and function, delved into the fascinating mechanisms that underlie taste transmission, shedding light on how sensory information is relayed from the taste buds to the brain, enabling us to perceive and differentiate various flavors.Result and Discussions: This narrative review indicates that diverse factors can induce changes in taste buds, ranging from genetic predispositions to external influences such as medications and lifestyle habits. By comprehensively understanding these factors, healthcare professionals and researchers can better identify the root causes of taste problems and devise effective management strategies. Recognizing the clinical significance of taste-related issues is crucial in providing appropriate care and support to individuals experiencing taste disorders.Conclusions: Despite significant advancements in understanding the gustatory function and molecular mechanisms of taste receptor cells, there still needs to be a comprehensive clinical understanding regarding the underlying causes and mechanisms of taste disorders in humans. Keywords: Tasting System - Taste Disorder – Gustatory - Clinical Significance

Korelasi ekspresi LMP-1 dengan ekspresi E-chaderin dan MMP-9 pada mekanisme metastasis penderita KNF WHO tipe 3 Adrian Benediktus; Soehartono Soehartono; Hendradi Surjotomo
Oto Rhino Laryngologica Indonesiana Vol. 49 No. 1 (2019): Volume 49, No. 1 January-June 2019
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32637/orli.v49i1.263

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.

Korelasi ekspresi IL-6 dengan STAT3 pada metastasis penderita KNF WHO tipe 3 LMP-1 positif S. Soehartono; Monika Teresa Prasetyo; Hendradi Surjotomo; Hendy Setyo Yudhanto
Oto Rhino Laryngologica Indonesiana Vol. 49 (2019): Volume 49, No. 2 July - December 2019
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32637/orli.v49i20.317

Latar belakang: Karsinogenesis karsinoma nasofaring sangat kompleks, dan disebabkan oleh interaksi antara infeksi kronis Epstein-Barr Virus (EBV), faktor lingkungan, dan perubahan genetik serta epigenetik. Latent Membrane Protein (LMP)-1 merupakan antigen utama EBV. LMP-1 diyakini menstimulasi ekspresi sitokin yang memengaruhi perilaku sel epitel, salah satunya adalah Interleukin (IL)- 6. IL-6 akan mengaktivasi jalur Signal Transducer and Activator of Transcription (STAT)3. Peningkatan ekspresi IL-6 dan STAT3 memiliki kaitan erat dalam lingkungan mikro tumor KNF, namun peran IL-6 dan STAT3 dalam modulasi migrasi dan invasi sel KNF masih belum jelas diketahui. Tujuan: Mengetahui korelasi antara ekspresi IL-6 dan ekspresi STAT3 di jaringan nasofaring dengan metastasis penderita KNF WHO tipe III LMP-1 positif. Metode: Penelitian observasional analitik dengan pendekatan cross-sectional yang melibatkan 15 penderita KNF WHO tipe III LMP-1 positif. Pemeriksaan ekspresi LMP-1, IL-6, dan STAT3 menggunakan metode pewarnaan imunohistokimia, dan hasilnya dihitung dengan menggunakan software ImmunoRatio. Penentuan stadium klinis metastasis berdasarkan pemeriksaan klinis dan penunjang radiologis, kemudian dievaluasi nilai TNM menggunakan AJCC 2017. Hasil: Analisis statistik ekspresi IL-6 dan STAT3 menunjukkan korelasi yang signifikan (p=0,020) dengan koefisien korelasi r=0,592. Tidak terdapat perbedaan ekspresi IL-6 yang bermakna di antara penderita stadium III, IVa, dan IVb (p=0,116). Terdapat perbedaan ekspresi STAT3 yang signifikan di antara penderita dengan stadium III, IVa, dan IVb (p=0,038). Kesimpulan: Semakin tinggi ekspresi IL-6 maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif semakin meningkat. Semakin tinggi stadium klinis, maka ekspresi STAT3 pada jaringan nasofaring penderita KNF WHO tipe III LMP-1 positif akan meningkat. Kata kunci: karsinoma nasofaring, Virus Epstein-Barr, LMP-1, IL-6, STAT3 ABSTRACT Background:Carcinogenesis of NPC is complex interactions among chronic EBV infection, environmental factors, genetic and epigenetic. LMP-1 is EBV’s antigen most expressed in NPC cases. LMP-1 is believed to stimulate expression of cytokines that affect the behavior of epithelial cells, i.e. Interleukin-6 (IL-6) which will activate the STAT3 pathway. Increased expression of IL-6 and STAT3 has a close relationship in tumor microenvironment of NPC patients, but the role of IL-6 and STAT3 themselves in modulation of migration and invasion of NPC cells are not yet fully understood. Purpose: To find out the correlation between IL-6 expression and STAT3 expression in the nasopharyngeal tissue of NPC patients with LMP-1 positive metastatic WHO type III. Method: Observational analytic study with cross-sectional approach involving 15 patients WHO type III LMP-1 positive NPC patients. Examination of LMP-1, IL-6, and STAT3 using immunohistochemical, and the results were calculated using ImmunoRatio. Clinical staging of metastases based on clinical examination and radiological imaging then synchronized with AJCC 2017. Result: Expressions of IL-6 and STAT3 showed significant correlation (p=0.020) with coefficient r=0.592. There were no differences in IL-6 expression among patients with stage III, IVa, and IVb (p=0.116). There were significant differences in STAT3 expression among patients with stage III, IVa, and IVb (p=0.038). Conclusion: There was a significant positive correlation between IL-6 and STAT3 in tissue from WHO type III LMP-1 positive NPC patients. The higher the clinical stage, the expression of STAT3 in the nasopharyngeal tissue of positive WHO type III LMP-1 NPC patients will increase.

Correlation of nodule with body mass index and Karnofsky status in nasopharyngeal carcinoma chemotherapy Bagus Harning Efranto; Soehartono -; Edi Handoko
Oto Rhino Laryngologica Indonesiana Vol. 51 No. 1 (2021): Volume 51, No. 1 January - June 2021
Publisher : PERHATI-KL

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32637/orli.v51i1.412

Background: Nasopharyngeal carcinoma (NPC) is a malignancy arising from the nasopharyngeal epithelium, usually present in the Rosenmüller fossa. NPC is a cancer of the head and neck that is most common in Indonesia. The main therapeutic for NPC is radiotherapy. Neoadjuvant chemotherapy reduces the local spread of advanced NPC, optimizing the eradication of micrometastases, and improved local control. Neoadjuvant chemotherapy’s effectiveness can be assessed by changes in the patient’s neck nodule size (N), Body Mass Index (BMI), and Karnofsky’s status. Purpose: To determine the correlation between N with BMI and Karnofsky status on neoadjuvant chemotherapy with Cisplatin and 5-Fu in WHO type 3 of NPC patients. Method: Analytical observational study using medical record data. An assessment of N, BMI and Karnofsky status of NPC WHO type 3 of 23 patients who had undergone neoadjuvant chemotherapy using Cisplatin and 5-Fu for three cycles. Result: The N value decreased, p = 0.001. BMI value decreased, p = 0.615. Karnofsky’s status value, p = 0.564. The correlation between N and BMI before and after three cycles of neoadjuvant chemotherapy: r = -0.201 and p = 0.358 ; r = -0.070 and p = 0.751. Correlation of N with Karnofsky status: r = 0.155 and p = 0.480; r = 0.571 and p = 0.004. Conclusion: Neoadjuvant chemotherapy with Cisplatin and 5-Fu was effective towards reducing the N and also in correlation between N and BMI but less effective in the correlation between N and Karnofsky status.ABSTRAK Latar belakang: Karsinoma nasofaring (KNF) adalah keganasan yang berasal dari epitel nasofaring yang biasanya timbul di fossa Rosenmüller. KNF merupakan kanker di kepala dan leher yang paling umum terjadi di Indonesia. Terapi utama pada KNF adalah radioterapi. Kemoterapi neoajuvan dapat menurunkan penyebaran lokal KNF stadium lanjut, mengoptimalkan eradikasi mikrometastasis, dan meningkatkan kontrol lokal. Efektivitas kemoterapi neoajuvan dapat dinilai dengan perubahan ukuran nodul leher (N) pasien, indeks massa tubuh (IMT) dan status Karnofsky pasien. Tujuan: Mengetahui korelasi antara N dengan IMT dan status Karnofsky pada pemberian kemoterapi neoajuvan Cisplatin dan 5-Fu pada pasien KNF WHO tipe 3. Metode: Penelitian observasional analitik dengan menggunakan data rekam medis. Penilaian dilakukan terhadap N, IMT dan status Karnofsky pada 23 pasien KNF WHO tipe 3 yang telah menjalani kemoterapi neoajuvan dengan menggunakan Cisplatin dan 5-Fu sebanyak tiga siklus. Hasil: Nilai N menurun, p=0,001. Nilai IMT menurun, p=0,615. Nilai status Karnofsky, p=0,564. Korelasi antara N dengan IMT sebelum dan setelah tiga siklus kemoterapi neoajuvan: r= -0,201 dan p= 0,358; r= -0,070 dan p=0,751. Korelasi N dengan status Karnofsky: r=0,155 dan p=0,480; r=0,571 dan p=0,004. Kesimpulan: Kemoterapi neoajuvan dengan Cisplatin dan 5-Fu efektif terhadap penurunan N serta korelasi antara N dengan IMT, namun kurang efektif menilai korelasi antara N dengan Status Karnofsky.Kata kunci: karsinoma nasofaring, kemoterapi neoajuvan,nodul, indeks massa tubuh, status Karnofsky

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