Research Article

Hubungan antara Tumor Infiltrating Lymphocytes (TIL), ekspresi Programmed Death-Ligan 1 (PD-L1) pada sel tumor dan TIL dengan kedalaman invasi pada karsinoma urotelial kandung kemih tipe tidak spesifik di RSUP Sanglah, Bali, Indonesia

Luh Ayu Widayanti , I Gusti Ayu Sri Mahendra Dewi, Herman Saputra, Anak Agung Ayu Ngurah Susraini, Ni Putu Sriwidyani, I Made Muliarta

Luh Ayu Widayanti
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia. Email: ayu.widayanti86@gmail.com

I Gusti Ayu Sri Mahendra Dewi
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia

Herman Saputra
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia

Anak Agung Ayu Ngurah Susraini
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia

Ni Putu Sriwidyani
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia

I Made Muliarta
Departemen Fisiologi, Fakultas Kedokteran, Universitas Udayana, Bali, Indonesia
Online First: December 01, 2020 | Cite this Article
Widayanti, L., Dewi, I., Saputra, H., Susraini, A., Sriwidyani, N., Muliarta, I. 2020. Hubungan antara Tumor Infiltrating Lymphocytes (TIL), ekspresi Programmed Death-Ligan 1 (PD-L1) pada sel tumor dan TIL dengan kedalaman invasi pada karsinoma urotelial kandung kemih tipe tidak spesifik di RSUP Sanglah, Bali, Indonesia. Intisari Sains Medis 11(3): 1119-1125. DOI:10.15562/ism.v11i3.806


Background: Urotelial carcinoma is one of carcinoma with increasing morbidity and mortality. The depth of invasion is one of risk factors that influence recurrence and survival rate in urotelial carcinoma. Patient with deeper invasion has poorer prognosis in recurrence and survival rate. Generally, carcinoma have microenvironment such as tumor infiltrating lymphocytes (TIL) to eliminate the tumor cells, in proliferative area. Cancer cells can avoid host immunity through PD-1/PD-L1 pathway. This study aimed to determine the association between TIL and PD-L1 expression with the depth of invasion of urotelial carcinoma.

Methods: This study was a cross sectional analytic study with 37 samples size. The samples were taken from paraffin block of patients with urotelial bladder carcinoma non-specific type, that has performed resection and histopathological examination at Anatomical Pathology Laboratory Sanglah Hospital Denpasar, from January 1st, 2015 to December 31th, 2019. Rediagnosis was carried out to assess the histopathological diagnosis, TIL and depth of invasion. Then PD-L1 immunohistochemistry was performed. Data were analyzed by Chi-Square test with p<0.05. Data were analyzed using SPSS version 20 for Windows.

Results: In this study on bladder urothelial carcinoma non-specific type at Sanglah Hospital Denpasar, we found there is no association between TIL and the depth of invasion (p=0.471). There is association between PD-L1 expression in tumor cells with the depth of invasion (p=0.006), OR 7.04 (CI 95% =1.64-30.20). There is association between PD-L1 expression in TIL with the depth of invasion (p=0.001), OR 13.2 (CI 95% = 2.62-66.43).

Conclusion: There is association between PD-L1 expression in tumor cells an PD-L1 expresion in TIL with the depth of invasion. Positive expression of PD-L1 in tumor cells and TIL are more likely to become advance invasion. Tumor Infiltrating Lymphocytes (TIL) and PD-L1 expression on TIL can be used as predictive factors for the depth of invasion in urotelial carcinoma.

 

 

Latar Belakang: Karsinoma urotelial merupakan salah satu karsinoma dengan morbiditas dan mortalitas yang terus meningkat. Salah satu faktor risiko yang mempengaruhi rekurensi dan survival rate pada karsinoma urotelial adalah kedalaman invasi. Invasi yang lebih dalam memiliki prognosis yang lebih buruk. Karsinoma umumnya disertai lingkungan mikro antara lain tumor infiltrating lymphocytes (TIL) yang berfungsi untuk mengeliminasi tumor. Sel kanker memiliki kemampuan untuk menghindari imun host antara lain melalui ikatan PD-1 dengan PD-L1. Tujuan dari penelitian ini untuk mengetahui hubungan antara TIL dan ekspresi PD-L1 dengan kedalaman invasi pada karsinoma urotelial.

Metode: Penelitian ini merupakan studi analitik potong lintang dengan besar sampel adalah 37, yang berasal dari blok parafin penderita karsinoma urotelial kandung kemih tipe tidak spesifik yang diperiksa histopatologi di Laboratorium Patologi Anatomi RSUP Sanglah Denpasar dari 1 Januari 2015 sampai 31 Desember 2019. Rediagnosis preparat dilakukan untuk menilai diagnosis histopatologi,  TIL serta kedalaman invasi. Kemudian dilakukan pulasan imunohistokimia PD-L1. Data dianalisis dengan uji Chi-Square dengan nilai p<0,05. Data dianalisis dengan SPSS versi 20 untuk Windows.

Hasil: Hasil penelitian ini menunjukkan bahwa pada karsinoma urotelial kandung kemih tipe tidak spesifik di RSUP Sanglah Denpasar, tidak terdapat hubungan yang signifikan antara TIL dengan kedalaman invasi (p=0,471). Terdapat hubungan yang signifikan antara ekspresi PD-L1 pada sel tumor dengan kedalaman invasi (p=0,006) dengan OR 7,04 (IK 95% =1,64-30,20), antara ekspresi PD-L1 pada TIL dengan kedalaman invasi (p=0,001) dengan OR 13,20 (IK 95% = 2,62-66,43).

Kesimpulan: Terdapat hubungan antara ekspresi  PD-L1 pada sel tumor dan pada TIL dengan kedalaman invasi pada karsinoma urotelial kandung kemih tipe tidak spesifik di RSUP Sanglah Denpasar. Ekspresi positif PD-L1 pada sel tumor dan pada TIL memiliki kemungkinan lebih besar untuk menjadi invasi lanjut.

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