Asosiasi antara mutasi gen p16 dengan tipe histopatologi karsinoma nasofaring

Abstract

Latar belakang: Pertumbuhan tumor dan metastasis penderita karsinoma nasofaring (KNF) yangdiduga karena peran beberapa biomarker molekular, dapat diidentifikasi dari spesimen tumor penderitaKNF. Inaktivasi gen p16 akibat mutasi gen p16 dapat digunakan sebagai indikator prognosis dan strategipemberian terapi yang lebih baik pada penderita KNF.Tujuan: Membuktikan asosiasi antara mutasi genp16 dengan tipe histopatologi KNF.Metode: Bahan biopsi dibagi menjadi 2 bagian untuk pemeriksaanhistopatologi dan polymerase chain reaction (PCR). Tipe histopatologi diketahui dari 21 tumor KNFdengan melakukan pengecatan hematoksilin eosin jaringan secara Meyer, terbagi 3 yaitu WHO tipe 1,tipe 2 dan tipe 3. Mutasi gen p16 diperiksa dari jaringan tumor primer KNF dengan PCR, menggunakanmesin Gene Touch Bioneer, dan sekuensing dengan mesin ABI PRISM 310. Analisis statistik menggunakanuji Spearman.Hasil: Didapati sebanyak 21 penderita KNF sesuai kriteria inklusi dan eksklusi. Diketahuisebanyak 19 penderita KNF (90,48%) mengalami mutasi gen p16 negatif. Sebanyak 2 penderita KNF(9,52%) mengalami mutasi gen p16 positif dengan histopatologi WHO tipe 3. Hasil uji Spearmanmendapatkan nilai p=0,568 dan koefisien korelasi sebesar –0,132. Asosiasi antara mutasi gen p16 dengantipe histopatologi (WHO tipe 1, 2, dan 3) pada penderita KNF didapatkan hasil yang tidak bermakna(p>0,05).Kesimpulan: Tidak terdapat asosiasi antara mutasi gen p16 dengan tipe histopatologi KNF.Hal tersebut mungkin oleh karena insidens mutasi gen p16 yang rendah dan faktor etnis.Kata kunci: Karsinoma nasofaring, mutasi gen p16, tipe histopatologi ABSTRACTBackground: Tumor growth and metastasis in nasopharyngeal carcinoma (NPC) patients whichwere presumed caused by the roles of several molecular biomarkers, could be identified in tumor specimensof NPC patients. P16 gene inactivation that was caused by mutation, can be used as an indicator ofprognosis and as strategy for better therapy in NPC. Purpose: To identify the association between p16 genemutation with type of histopathology NPC. Methods: Biopsy specimens were divided for histopathologyexamination and polymerase chain reaction (PCR). Type of histopathology was obtained from 21 NPCtumors by Meyer’s hematoxillin eosin staining, and divided into three types, WHO type 1, type 2 andtype 3. The mutation of p16 gene were identified with PCR from primary tumor tissues by using Bioneertermal cycler machine, and sequencing was performed by ABI PRISM 310. Spearman test was used forstatistical analysis. Results: We found 21 NPC patients who met the inclusion and exclusion criteria.There were 19 (90.48%) NPC patients which had negative mutation of p16 gene. There were 2 NPCpatients (9.52%) who had positive mutation of p16 gene, with histopathology WHO type 3. Spearmantest results showed P=0.568 with a correlation coefficient –0.132. Association of mutation of p16 genewith histopathology type (WHO type 1, 2, 3) in NPC patients was not significant (P>0.05). Conclusion:There was no association found in our study between mutation of p16 gene and histopathological typeof nasopharyngeal carcinoma. It might be caused by low incidence of gene p16 mutation in NPC, andethnic factor.Keywords: Nasopharyngeal carcinoma, mutation of p16 gene, histopathology type