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"Latar belakang: Pada kanker nasofaring, tingginya angka kegagalan metastasis jauh paska terapi masih menimbulkan masalah. Sehingga, penelitian mengenai penggunaan terapi sistemik novel pada kanker nasofaring seperti imunoterapi perlu dilakukan. Terdapat beberapa biomarker yang dapat diperiksa untuk dapat memprediksi respon dari pemberian imunoterapi, salah satunya adalah microsatellite instability (MSI). Mikrosatelit merupakan area pada DNA yang memiliki banyak pengulangan kodon, sehingga rentan terjadi gangguan coding dan mengakibatkan akumulasi mutasi. Pada keadaan normal, kerusakan ini akan diperbaiki dengan sistem mismatch repair. Namun, jika terdapat gangguan atau mutasi terkait sistem ini, atau yang disebut dengan deficient mismatch repair (dMMR), akan menghasilkan fenotipe MSI. Pada kanker kolorektal dan endometrium. Namun sampai saat ini, hanya terdapat 3 penelitian yang melakukan pemeriksaan status MSI pada kanker nasofaring. Penelitian ini bertujuan untuk melihat gambara status MSI pada pasien kanker nasofaring pada pasien di RSCM, Indonesia.Metode: Penelitian ini merupakan penelitian eksploratif dengan 36 subjek penelitian. Dilakukan pemeriksaan status instabilitas mikrosatelit menggunakan pemeriksaan berbasis polymerase chain reaction (PCR) Idylla MSI. Dilakukan pula pemeriksaan MMR menggunakan pemeriksaan berbasis imunohistokimia (IHK) menggunakan 4 antibodi untuk mendapatkan keselerasan antara pemeriksaan MSI dan MMR pada pasien kanker nasofaring di RSCM.Hasil : Menggunakan pemeriksaan Idylla MSI, ditemukan MSI pada 2 dari 36 pasien (5,6%) dan dMMR menggunakan pemeriksaan IHK pada 3 dari 36 pasien (8,34%). Hasil yang konsisten ditemukan pada 2 metode pemeriksaan sebesar 96,97%.Kesimpulan: Pada kanker nasofaring ditemukan frekuensi MSI yang rendah baik menggunakan pemeriksaan IHK dan Idylla MSI. Ditemukan keselerasan yang tinggi antara pemeriksaan berbasis IHK dan pemeriksaan berbasis PCR Idylla MSI.

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Background: Despite high probability of local control after treatment, high rate of distant metastases-failure still pose as problem in the management of locally advanced nasopharyngeal carcinoma. Thus, research for novel systemic therapies for nasopharyngeal cancer, such as immunotherapy, needs to be done. There are several biomarkers that may predict the response to immunotherapy, one of which is microsatellite instability (MSI) phenotype. Microsatellites defined by areas in DNA that are prone to mutations due to repetition of 1-3 nitrogen base. However, under normal circumstances, there are repair systems that can identify and correctly repairs DNA mutations in microsatellite area, a system called mismatch repair (MMR) system. Microsatellite instability is a condition of accumulating mutations in microsatellite area due to defect in MMR system. In colorectal and endometrial cancer, MSI are known as one of prognostic and predictive markers, especially with the usage of immunotherapy immune checkpoint blockade PD-1/PD-L1. To this date, only 3 studies are available in exploring the role of MSI in nasopharyngeal cancer, and no study was done in Indonesia. We conduct this study to assess the MSI status of Indonesia's nasopharyngeal cancer patients in Ciptomangunkusumo Hospital.

Methods: This is the first explorative study in exploring the role of MSI in Indonesia's nasopharyngeal cancer patients. A total of 36 subjects were recruited, and both MSI assessment using immunohistochemistry (IHC) and polymerase chain reaction (PCR) Idylla MSI was done on all study subjects.

Results: MSI was found in 2 patients (5,6%) using PCR based Idylla MSI, and dMMR was found in 3 patients (8,34%). Consistent results between IHC and PCR based MSI assessment was found in 32 patients (96,97%).

Conclusion: MSI was a rare event in Indonesia's nasopharyngeal cancer patients. High concordance was found between IHC and PCR MSI assessment in nasopharyngeal cancer."

"Latar belakang: Kanker nasofaring merupakan keganasan yang unik dimana angka kejadiannya termasuk jarang disebagian besar negara, namun endemis di wilayah tiongkok selatan, dan asia tenggara termasuk Indonesia. Histopatologi kanker nasofaring di daerah endemik biasanya merupakan karsinoma jenis tidak berkeratin tidak berdiferensiasi dan selalu terkait dengan infeksi EBV. Berbagai jenis protein virus diekspresikan pada infeksi laten EBV termasuk EBNA1 dan LMP1 mungkin berkontribusi dalam perkembangan kanker. Oleh karenanya, kami ingin menginvestigasi peran onkoprotein virus tersebut terhadap agresivitas dan respon terapi kanker nasofaring. Metode: Spesimen biopsi jaringan dan darah yang diambil dari pasien kanker nasofaring diukur kadar EBNA1 dan LMP1 dengan menggunakan pemeriksaan ELISA kit masing-masing dari DRG® dan MyBioSource® kemudian dikorelasikan dengan voume tumor dan KGB terlibat yang dinilai berdasarkan delineasi berbasis pencitraan 3D. Pasien kemudian menjalani terapi standar, dan dilakukan penilaian 3 bulan paska terapi. Respon terapi akan dinilai hubungannya dengan kadar EBNA1 dan LMP1. Hasil: 23 subjek dimasukan kedalam studi, 69,5% berada pada stadium IVA keatas, dengan mayoritas laki-laki sebanyak 61%. Median volume tumor primer dan volume KGB masing masing 41,4cc (13,2-128,8) dan 40,1cc (1,2-633,5). Uji korelasi Spearman mendapatkan hubungan bermakna (p=0,032) antara kadar LMP1 jaringan dan volume tumor sebelum terapi (r=0,448). Tren korelasi yang moderat terlihat pada kadar EBNA1 di jaringan dengan di darah, kadar EBNA1 di jaringan dengan volume tumor primer, kadar EBNA1 di darah dengan volume KGB, serta Kadar LMP1 baik di jaringan maupun di darah dengan volume KGB, meskipun secara keseluruhan tidak bermakna secara statistik. Sementara itu, pengaruh kadar LMP1 dan EBNA1 terhadap respon terapi belum dapat disimpulkan. Kesimpulan: Semakin tinggi kadar LMP1 di jaringan tumor akan diikuti oleh semakin besarnya volume tumor primer nasofaring. Korelasi moderat tidak signifikan pada variabel lain mungkin diakibatkan oleh jumlah sampel yang kurang. Penambahan besar sampel diperlukan untuk konfirmasi signifikansi dari korelasi tersebut.

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Background: Nasopharyngeal cancer is an unique malignancy where the incidence is rare in most countries but endemic in Southern China and Southeast Asia, including Indonesia. The histopathology of nasopharyngeal cancer in endemic areas is usually an undifferentiated nonkeratinizing type carcinoma and is always associated with EBV infection. Various viral proteins are expressed in latent EBV infection, including EBNA1 and LMP1. These viral oncoproteins may contribute to cancer development, but they are not always be defined. Therefore, we want to investigate the role of these viral oncoproteins when it comes to the aggressivity and treatment response of nasopharyngeal cancer.

Methods: Tissue biopsy and blood specimens taken from nasopharyngeal cancer patients were measured for EBNA1 and LMP1 using the ELISA kit examination from DRG® and MyBioSource® respectively, then correlated with primary tumor and nodal volume, which was calculated by delineation based on 3D imaging. Patients then underwent standard therapy, and was assessed 3 months post-therapy. Response to therapy will be assessed in relation to levels of EBNA1 and LMP1.

Results: 23 subjects were included in the study, 69.5% was at stage IVA and above with the majority being males (61%). The median primary tumor and lymph node volume were 41.4cc (13.2-128.8) and 40.1cc(1,2-633.5), respectively. Spearman correlation test found a significant relationship (p=0.032) between tissue LMP1 levels and tumor volume before therapy (r=0.448). A moderate correlation trend was seen in EBNA1 levels in tissue with blood, EBNA1 levels in tissue with primary tumor volume, EBNA1 levels in blood with lymph node volume, and LMP1 levels both in tissue and in blood with lymph node volume, although overall it was not statistically significant. Meanwhile, the effect of LMP1 and EBNA1 levels on the response to therapy cannot be concluded.

Conclusion: The higher the level of LMP1 in the tumor tissue, the larger the volume of primary nasopharyngeal tumor will be. Moderately insignificant correlation on the other variables may be caused by a small number of samples. The addition of the sample size is needed to confirm the significance of the correlation."