HUBUNGAN EKSPRESI PD-L1 DENGAN GRADING TUMOR, INDEKS PROLIFERASI, DAN TUMOR- INFILTRATING LYMPHOCYTES (TILs) PADA KARSINOMA UROTELIAL KANDUNG KEMIH

TH. HENING DWI A, dr. Hanggoro Tri Rinonce, Sp.PA(K), Ph.D; dr. Paranita Ferronika, Sp.PA(K),Ph.D

2021 | Tesis-Spesialis | PATOLOGI ANATOMI

Latar belakang: Karsinoma urotelial merupakan kanker kandung kemih terbanyak. Mortalitas kanker ini tidak menurun dengan terapi cisplatin berbasis platinum, sehingga diperlukan terapi alternatif. Saat ini dikembangkan terapi berupa agen penghambat checkpoint antara lain anti PD-L1 (Progammed Death Ligan 1). Profil ekspresi PD-L1 yang tinggi berkaitan dengan grading tumor, indeks proliferasi dan tumor-infiltrating lymphocyte (TILs) pada karsinoma urotelial kandung kemih di Indonesia belum banyak dikembangkan. Objektif: Mengetahui ekspresi PD-L1 pada karsinoma urotelial kandung kemih dan dengan berbagai parameter patologik, yaitu grading tumor, indeks proliferasi dan TILs. Metode : Tujuh puluh blok parafin karsinoma urotelial kandung kemih dari RSUP Dr. Sardjito Yogyakarta tahun 2015-2019 dipilih sebagai sampel dan diperiksa ekspresi PD-L1 dan Ki-67 dengan metode imunohistokimia. PD-L1 and Ki-67. Ekspresi PD-L1 ditentukan dengan combined positive score (CPS). Antibodi PD-L1 menggunakan klon 22C3. Grading tumor dan TILs diamati pada sediaan HE dan dikelompokkan dalam low atau high-grade, TILs dinyatakan dalam intense (�10%) dan non-intense (<10%). Indeks proliferasi dinilai dengan menghitung jumlah sel yang positif Ki-67 per 1.000 sel dan dinyatakan dalam persentase. Hasil dianalisis menggunakan uji korelasi Spearman dengan perangkat lunak IBM SPSS 25. Hasil: PD-L1 terekspresi pada 8,57% kasus. Jumlah high-grade urothelial carcinoma lebih banyak (85,71%) dibandingkan dengan low-grade urothelial carcinoma. (14,28%). Jumlah sampel dengan TILs intense sebanyak 46 (65,71%) dan TILs non-intense 24 (34,28%). Ekspresi PD-L1 secara signifikan berhubungan dengan indeks proliferasi (p=0.043) dan TILs (p=0,032). Namun, tidak didapatkan hubungan yang signifikan dengan grading tumor (p = 0.236). Kesimpulan : Ekspresi PD-L1 pada karsinoma urotelial kandung kemih berhubungan secara signifikan dengan indeks proliferasi dan TILs, namun tidak dengan grading tumor.

Background: Urothelial carcinoma is the most common bladder cancer. Mortality has not decreased with combination cisplatinum-based chemotherapy, so alternative therapies are needed. The recently suggested therapy includes immune checkpoint inhibiting agents including anti PD-L1 (Programmed Death Ligand 1). High expression of PD-L1 in bladder cancer was suggested to be associated with HG, disease recurrence, and decreased survival. However, the PD-L1 expression profile among urotelial carcinoma cases in Indonesia and its association with pathological parameters are not widely studied. Objective: Determining the expression of PD-L1 in urotelial carcinoma of the bladder at Dr. Sardjito Hospital, Yogyakarta and its association with pathological parameters; grading tumor, proliferation index and tumor-infiltrating lymphocytes (TILs). Methods: Seventy formalin-fixed paraffin embedded (FFPE) tissue diagnosed with urothelial bladder carcinoma from Sardjito Hospital in 2015-2019 were consecutively selected as samples and examined PD-L1 expression and Ki-67 with immunohistochemistry. PD-L1 expression was determined by a combined positive score (CPS). PD-L1 antibody was using Clone 22C3. Tumor grade and TILs were observed in HE staining and divided into low or high-grade based on morphology, TILs is grouped into intense (� 10%) and non-intense (<10%). The proliferation index was assessed by counting the number of Ki-67 positive cells per 1,000 tumor cells and presented as a percentage. The results were analysed using the Spearman correlation with the IBM SPSS 25 application. Result: PD-L1 was expressed in 8.57% of cases. The number of samples with intense TILs was 46 (65.71%) and 24 (34.28%) non-intense TILs. PD-L1 expression was significantly associated with the proliferation index (p = 0.043) and TILs (p = 0.032). It was significantly correlated with proliferative index (p=0.043) and TILs (p=0.032), but not correlated with tumor grade (p =0.236). Conclusion : PD-L1 expression in urothelial carcinoma of the bladder was significantly associated with proliferation index and TILs, but not with tumor grade.

Kata Kunci : urothelial carcinoma, PD-L1 IHC 22C3, proliferation index, grading tumor, tumor-infiltrating lymphocyte