ABSTRAK
Biomarka untuk memprediksi metastasis KGB lokoregional sampai saat ini belum akurat.Angka metastasis tersamar pada karsinoma laring bervariasi yaitu 165%. Dibutuhkanbiomarka tumor yang dapat memberikan informasi adanya metastasis KGB lokoregionalpada pasien KSS laring stadium lanjut tanpa keterlibatan KGB lokoregional (N0), sehinggadiharapkan menjadi acuan untuk dilakukan diseksi leher selektif. Beberapa biomarka yangberhubungan dengan agresivitas dan prediksi metastasis yaitu Epidermal Growth FactorReceptor (EGFR), Matrix Metallo-proteinase (MMP)-9, Tissue Inhibitor Metallproteinase(TIMP)-1, Vascular Endothelial Growth Factor (VEGF), Epithel Calcium Adhesi (Ekaderin)dan kolagen tipe IV serta HPV dapat digunakan untuk memprediksi luaran padastatus pasien tumor dengan dan tanpa metastasis.Penelitian ini ingin memeriksa peran infeksi HPV sebagai faktor onkogenesis dankejadian metastasis KGB leher pada keganasan laring berdasarkan biomarka sebagaipenetapan diagnosis metastasis KGB lokoregional.Dilakukan Cross-sectional, double blind study dengan pengumpulan data sekunder darirekam medis di Departemen THT-KL FKUI-RSCM. Pemeriksaan ekspresi biomarkadan status HPV dilakukan terhadap jaringan berupa blok parafin dari pasien karsinomalaring Ekspresi biomarka dilakukan dengan pemeriksaan imunohistokimia, dan identifikasivirus HPV dengan nested PCR, dilanjutkan dengan flow-through hybridization.Didapatkan proporsi HPV KSS laring sebanyak 28,7% dengan infeksi HPV risiko tinggisebanyak 9,15% dan HPV 16 merupakan tipe yang terbanyak. Analisis multivariatMantel-Haenszel didapatkan ekspresi tinggi biomarka EGFR, MMP-9 dan VEGFberperan terhadap kejadian metastasis KGB pada KSS laring stadium lanjut tanpainfeksi HPV dengan OR 3,38; 5,14. Keadaan tersebut tidak berperan lagi bila terdapatinfeksi HPV Dari penelitian ini didapatkan suatu algoritma penatalaksanaan KSS laringstadium lanjut khususnya untuk penentuan tatalaksana diseksi leher pada N0.Infeksi HPV didapati pada KSS laring stadium lanjut, HPV 16 merupakan tipe HPVyang terbanyak. Biomarka penanda metastasis didapatkan pada EGFR; MMP-9; VEGFdengan kekuatan 2;1;6.
ABSTRACT
Biomarkers to predict locoregional lymph nodes metastasis is not yet accurate untilnow. The number of occult metastasis in laryngeal carcinoma varies between 165%.A tumor biomarker that can give information on the existence of locoregional lymphnode involvement in patients with or without signs of clinical locoregional lymph nodeinvolvement, as guidelines whether selective neck dissection is needed in N0 cases. Forpatients that need additional treatment biomarkers that are correlated with aggresivityand metastasis prediction such as EGFR, MMP-9, TIMP-1, VGEF, E-cadherin, collagenType IV and HPV are also needed to predict the outcome of patients with or withoutlymph node metastasis.This study aimed to investigate the evidence of HPV infection in laryngeal carcinomaand the role of biomarkers EGFR, MMP-9, TIMP-1, VEGF, E-cadherin and collagentype IV, in a late stadium laryngeal SCC observed clinically, especially in N0 and alsoto predict diagnosis of a locoregional lymph node that has potential for metastasis.Cross-sectional, double blind study with planned data collection was performed in theDepartment of ENT FKUI-RSCM. Data were taken from Formalin Fixed ParaffinEmbedded (FFPE) of laryngeal cancer specimen after laryngectomies. Samples wereanalysed by nested Polymerase Chain Reaction (PCR) and continuous flow-throughhybridizationed for genotyping. Expression of EGFR, MMP-9, TIMP-1, VEGF, Ecadherin,and collagen Type IV as metastasis biomarker were evaluated byimmunohistochemistry.Overall HPV proportion in laryngeal cancer was 28.7%. A total of 9,15% laryngealcancer patients were infected with high risk HPV type and HPV 16 was the mostfrequently observed. Mantel-Haenszel multivariate analysis found that HPV infection didnot play role in neck metastasis eventhough there were positive evidence of metastasisbiomarker. In contrast, the absent of HPV infection, positif metastasis biomarker of EGFRand VEGF have risk for neck nodes metastasis with OR 3.38; 5.14 fold consecutively.The algorithm was formed from the PM model to determine the metastasis potential tolocoregional lymph nodes of late stadium laryngeal SCC with N0.HPV was found to be the oncogenic factor of the laryngeal SCC and HPV 16 was themost frequently observed type in laryngeal SCC. Biomarkers to predict locoregionallymph nodes metastasis are EGFR; VEGF with strenght 2;1;6. |
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