Kusuma, Ihda Dian and dr. Diah Prabawati Retnani,, SpPA(K), and dr .Hendy Setyo Yudhanto,, SpPA and dr Harun Al Rasyid,, MPH (2022) Korelasi Ekspresi Latent membrane protein-1 (LMP-1) dengan Ekpresi B-cell lymphoma/leukemia 11B (BCL11B) pada Karsinoma Nasofaring. Magister thesis, Universitas Brawijaya.
Abstract
Karsinoma Nasofaring (KNF) adalah karsinoma sel skuamosa yang terjadi pada lapisan epitel nasofaring. Karsinoma Nasofaring merupakan keganasan endemik di Asia dengan insidensi dan mortalitas tinggi, termasuk di Indonesia. Etiologi KNF di daerah endemik, salah satunya di Indonesia, adalah Epstein-Barr Virus (EBV). Jenis karsinoma nasofaring yang berkaitan erat dengan infeksi EBV adalah undifferentiated carcinoma. Latent membrane protein-1 (LMP-1) adalah suatu onkoprotein utama dari Epstein-Barr Virus (EBV) yang telah diketahui berperan penting dalam tumorigenesis akibat virus melalui berbagai dugaan mekanisme. BCL11B dikenal sebagai faktor transkripsi yang diketahui memiliki peran dan fungsi dalam berbagai sel, diantaranya dapat berperan sebagai tumor suppressor gene, dan berpengaruh pada lingkungan mikro tumor, serta diekspresikan pada cancer stem cell yang berperan penting pada resistensi terapi. BCL11B telah diteliti dan terbukti berperan penting dalam tumorigenesis limfoma akibat virus HTLV1. Selain itu, juga terbukti berkorelasi positif dengan stadium tumor kepala leher. Penelitian mengenai peran LMP-1 pada patogenesis KNF telah banyak dilakukan, namun didapatkan hasil yang bervariasi karena ekspresinya yang bervariasi pula, sedangkan ekspresi BCL11B pada KNF belum pernah dipublikasikan. Penelitian ini bertujuan untuk menganalisis ekspresi LMP-1, ekspresi BCL11B pada sediaan KNF tipe undifferentiated carcinoma dan hubungan antara keduanya. Penelitian ini adalah penelitian dasar yang diharapkan dapat memberikan gambaran mengenai ekspresi BCL11B pada KNF sehingga didapatkan pemahaman patogenesis KNF lebih baik. Harapannya, dapat dikembangkan untuk penelitian selanjutnya terutama memahami tumorigenesis akibat virus. Implikasi klinis saat ini tidak bersifat langsung, namun dapat dikembangkan untuk mengetahui prognosis serta sebagai marker evaluasi terapi. Penelitian ini bersifat observasional analitik dengan desain cross sectional. Sampel dan kegiatan penelitian diperoleh dan dilakukan di Instalasi Patologi Anatomi RSUD dr Saiful Anwar Malang, dari blok parafin pasien yang didiagnosis KNF tipe undifferentiated carcinoma antara tahun 2018-2020. Didapatkan 30 sampel dari biopsi nasofaring pasien KNF tipe undifferentiated carcinoma. Pada penelitian ini, 30 sampel KNF yang diteliti sebagian besar berasal dari pasien laki-laki (70%) dan pada kelompok usia di atas 40 tahun (43,3%). Ekspresi LMP-1 secara immunohistokimia didapatkan hasil positif pada seluruh sampel KNF dengan persentase rata-rata 87,007 %. dengan persentase terendah 81% dan persentase tertinggi 92 %. Ekspresi BCL11B pada penelitian ini sangat rendah. Rata-rata persentase ekspresi protein BCL11B pada sediaan yang diperiksa adalah 0,35 % dengan persentase terendah 0% atau hasil negatif dan persentase tertinggi 1,6 %. Korelasi antara ekspresi LMP-1 dengan ekspresi BCL11B pada jaringan biopsi KNF tipe undifferentiated carcinoma dianalisis menggunakan uji korelasi Spearman. Hasilnya didapatkan nilai koefisien korelasi sebesar -0,511 dengan nilai signifikansi (p) sebesar 0,004 yang lebih kecil dari alpha 0,05, sehingga dapat disimpulkan bahwa terdapat korelasi yang signifikan antara ekspresi LMP-1 dengan ekspresi BCL11B pada jaringan biopsi nasofaring v penderita KNF undifferentiated dengan arah korelasi bernilai negatif dan kekuatan sedang yang artinya semakin tinggi ekspresi LMP-1, maka akan selaras dengan semakin rendahnya ekspresi BCL11B. Hasil penelitian ini menunjukkan bahwa infeksi EBV merupakan faktor risiko dalam kasus KNF. Belum ada penelitian yang secara khusus meneliti ekspresi BCL11B pada epitel nasofaring normal maupun KNF. Berdasarkan data yang ada, ekspresi BCL11B terbukti rendah pada epitel nasofaring normal, namun memang terdapat trend penurunan ekspresi protein BCL11B pada KNF. Meskipun kekuatan korelasi antara kedua ekspresi protein tersebut sedang, adanya hubungan antara keduanya tidak dapat diabaikan. Belum didapatkan cukup bukti yang menunjukkan bahwa LMP-1 mengganggu fungsi BCL11B sehingga menyebabkan KNF, sehingga masih diperlukan penelitian lebih lanjut untuk membuktikan hal tersebut
English Abstract
Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma that occurs in the epithelial lining of the nasopharynx. Nasopharyngeal carcinoma is an endemic malignancy in Asia with a high incidence and mortality, including in Indonesia. The etiology of NPC in endemic areas, one of which is in Indonesia, is Epstein-Barr Virus (EBV). Undifferentiated carcinoma is a type of nasopharyngeal carcinoma that is closely linked to EBV infection. Epstein-Barr virus (EBV) related Latent membrane protein-1 (LMP-1) is a major oncoprotein that has been shown to play a significant role in viral tumorigenesis through a variety of suspected mechanisms. BCL11B is a transcription factor that is known to play a variety of roles and functions in various cells. These roles and functions include being able to act as a gene that suppresses tumors, influencing the microenvironment of tumors, and being expressed in cancer stem cells that are important for therapeutic resistance. It has been discovered through research that the HTLV1 virus induces lymphoma tumorigenesis via BCL11B. It was also demonstrated to have a positive correlation with the head and neck tumor's stage. While the expression of BCL11B in NPC has never been published, numerous studies on the role of LMP-1 in the pathogenesis of NPC have been conducted. However, various results have been obtained due to its varying expression. The purpose of this research is to investigate the connection between the expression of BCL11B and LMP-1 in NPC preparations of the undifferentiated carcinoma type. To acquire a deeper comprehension of the pathogenesis of NPC, this basic research is expected to provide an overview of the expression of BCL11B in NPC. It is hoped that it will be able to be developed for additional research, particularly into viral tumorigenesis. Although the current clinical implications are not direct, they can be developed for the purpose of determining the prognosis and serving as a marker for the evaluation of therapeutics. The design of this study is cross-sectional analytic observational. At the Anatomical Pathology Laboratorium of RSUD Dr. Saiful Anwar Malang, samples and research activities were obtained from the paraffin blocks of patients diagnosed with undifferentiated carcinoma type NPC between 2018 and 2020. The nasopharyngeal biopsy of 30 patients with undifferentiated carcinoma type NPC yielded 30 samples. The majority of the 30 NPC patients studied in this study were male (70%) and over 40 years old (43.3%). Immunohistochemical expression of LMP-1 was positive in all NPC samples with an average percentage of 87,007%. with the lowest percentage of 81% and the highest percentage of 92%. The expression of BCL11B in this study was very low. The average percentage of BCL11B protein expression in the preparations examined was 0.35% with the lowest percentage being 0% or negative results and the highest percentage being 1.6%. The correlation between LMP-1 expression and BCL11B expression in undifferentiated carcinoma NPC biopsy tissue was analyzed using the Spearman correlation test. There is a significant correlation between LMP-1 expression and BCL11B expression in nasopharyngeal biopsy tissue of undifferentiated NPC patients with the direction of the correlation is negative and has moderate vii strength, indicating that the higher the LMP-1 expression, the lower the BCL11B expression will be. The results obtained a correlation coefficient value of -0.511 with a significance value (p) of 0.004, which is smaller than alpha 0.05. According to the findings of this study, EBV infection is the most significant risk factor for NPC cases. BCL11B expression in NPC or normal nasopharyngeal epithelium has not been the subject of any studies. The fact that the normal nasopharyngeal epithelium lacked BCL11B expression from the available data suggests that BCL11B protein expression was decreasing in NPC. The existence of a relationship between the two protein expressions cannot be ignored, despite the moderate strength of the correlation. However, further research is required to demonstrate that LMP-1 disrupts BCL11B function and causes NPC because there is insufficient evidence to support this claim.
Other obstract
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| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | 0422060157 |
| Uncontrolled Keywords: | korelasi, LMP-1, BCL11B, karsinoma nasofaring |
| Subjects: | 600 Technology (Applied sciences) > 616 Diseases > 616.2 Diseases of respiratory system > 616.24 Diseases of Lungs / Lungs--Diseases |
| Divisions: | Profesi Kedokteran > Spesialis Patologi Klinik, Fakultas Kedokteran |
| Depositing User: | Endang Susworini |
| Date Deposited: | 08 May 2023 01:56 |
| Last Modified: | 08 May 2023 01:56 |
| URI: | http://repository.ub.ac.id/id/eprint/198814 |
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