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Ekspresi Matrix Metalloproteinase-9 (MMP-9) dan Programmed Death Ligand-1 (PD-L1) pada karsinoma urotelial kandung kemih dengan invasi otot lebih tinggi dibandingkan karsinoma urotelial kandung kemih tanpa invasi otot

  • I Wayan Juli Sumadi ,
  • Dandy Citra ,
  • I Gusti Alit Artha ,


Background: The incidence of bladder cancer in Bali has increased in the last 5 years and ranks fifth as the most common cancer in Bali. The presence of invasion of the muscularis propria is considered the most important prognostic parameter in predicting the prognosis and determining the management of bladder carcinoma. However, nearly 50% of bladder carcinoma biopsy specimens are inadequate to determine the presence of muscle invasion. Based on this, it is necessary to develop predictive biomarkers for muscle invasion in bladder carcinoma. The biomarkers that may be associated as predictors of muscle invasion are MMP-9 and PD-L1. The objective of the study is to prove that there are differences in the expression of MMP-9 and PD-L1 in muscle-invasive bladder cancer compared to non-invasive bladder cancer.

Methods: This research is a cross-sectional analytical study involving 43 paraffin block samples from bladder carcinoma patients in the 2016-2020 period who underwent an examination in the Anatomical Pathology laboratory of Sanglah Hospital Denpasar. An immunohistochemical examination was carried out to assess the expression of MMP-9 and PD-L1, and the Chi-Square Test statistical test was carried out.

Results: It was found that the expression of MMP-9 and PD-L1 was significantly higher in muscle-invasive bladder carcinoma compared to non-muscle-invasive bladder carcinoma (p < 0.001).

Conclusion: There are significant differences in the expression of MMP-9 and PD-L1 in muscle-invasive bladder cancer compared to non-muscle-invasive bladder cancer. These two biomarkers have the potential to be used in predicting the presence or absence of muscle invasion in bladder carcinoma.


Latar Belakang: Insiden kanker kandung kemih di Bali mengalami peningkatan dalam 5 tahun terakhir dan menempati urutan ke lima sebagai kanker tersering di Bali. Adanya invasi pada otot polos muskularis propria dianggap sebagai parameter prognostik yang paling penting dalam meramalkan prognosis dan menentukan manajemen karsinoma kandung kemih. Namun, hampir 50% spesimen biopsi karsinoma kandung kemih tidak adekuat untuk menentukan adanya invasi otot. Berdasarkan hal tersebut maka perlu dikembangkan biomarker prediktif invasi otot pada karsinoma kandung kemih. Adapun biomarker yang kemungkinan dapat dihubungkan sebagai prediktor invasi otot adalah ekspresi MMP-9 dan ekspresi PD-L1. Penelitian ini bertujuan untuk membuktikan adanya perbedaan ekspresi MMP-9 dan PD-L1 pada karsinoma dengan invasi otot dan tanpa invasi otot pada karsinoma kandung kemih.

Metode: Penelitian ini merupakan penelitian analitik potong lintang yang melibatkan 43 sampel blok paraffin dari pasien karsinoma urotelial kandung kemih pada periode tahun 2016-2020 yang menjalani pemeriksaan di laboratorium Patologi Anatomi RSUP Sanglah Denpasar. Dilakukan pemeriksaan imunohistokimia untuk menilai ekspresi MMP-9 dan PD-L1 dan dilakukan uji statistik Chi Square Test.

Hasil: Didapatkan bahwa ekspresi MMP-9 dan PD-L1 lebih tinggi secara bermakna pada karsinoma kandung kemih dengan invasi otot dibandingkan non invasi otot dengan nilai p < 0,001.

Simpulan: Terdapat perbedaan ekspresi MMP-9 dan PD-L1 pada karsinoma kandung kemih dengan invasi otot dibandingkan tanpa invasi otot. Kedua biomarker ini potensial untuk digunakan dalam memprediksi ada tidaknya invasi otot pada karsinoma kandung kemih.


  1. Bray F, Ferlay J, Soerjomataram I. Global Cancer Statistics 2018 : GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 2018;00(00):1–31.
  2. Laporan Registrasi Kanker RSUP Prof. Dr. I.G.N.G Ngoerah. No Title. 2018.
  3. Grignon D, Al-Ahmadie H, Algaba F, Amin M., Comperat E, Dyrskjot L, et al. Urothelial tumours Infiltrating urothelial carcinoma. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th ed. Lyon: IARC; 2016;1(1):81–98.
  4. Witjes JA, Compérat E, Cowan NC, Santis M De, Gakis G, Lebrét T, et al. EAU Guidelines on and Metastatic Bladder Cancer. 2016;59(6):1009-1018.
  5. Chamie K, Ballon-Landa E, Bassett JC, Daskivich TJ, Leventhal M, Deapen D, et al. Quality of diagnostic staging in patients with bladder cancer: A process-outcomes link. Cancer. 2015;121(3):379–385.
  6. Babjuk M, Böhle A, Burger M, Compérat E, Kaasinen E, Palou J, et al. EAU Guidelines on Bladder Cancer. 2016;71(3):1–45.
  7. Sanguedolce F, Bufo P, Carrieri G, Cormio L. Predictive markers in bladder cancer: Do we have molecular markers ready for clinical use? Crit Rev Clin Lab Sci. 2014;51(5):291–304.
  8. Kumar V, Abbas A., Aster JC. Neoplasia. In: Kumar V, Abbas A., Aster JC, editors. Robbins and Cotran: Pathologic Basis of Disease. 10th ed. Philadelphia: Saunders; 2018;8(1):310–313.
  9. Huang H. Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances. 2018;9(1):5–7.
  10. Mehner C, Hockla A, Miller E, Ran S, Radisky DC, Radisky ES. Tumor cell-produced matrix metalloproteinase 9 ( MMP-9 ) drives malignant progression and metastasis of basal-like triple negative breast cancer. Oncotarget. 2014;5(9):2736.
  11. Oguić R, Mozetič V, Cini Tešar E, Fučkar Čupić D, Mustać E, Đorđević G. Matrix metalloproteinases 2 and 9 immunoexpression in prostate carcinoma at the positive margin of radical prostatectomy specimens. Pathology Research International. 2014;1(1):1-9.
  12. Braun MW, Iwakuma T. Regulation of cytotoxic T-cell responses by p53 in cancer. Transl Cancer Res. 2016;5(6):692–697.
  13. Sorensen SF, Zhou W, Dolled-Filhart M, Georgsen JB, Wang Z, Emancipator K, et al. PD-L1 expression and survival among patients with advanced non–small cell lung cancer treated with chemotherapy. Transl Oncol. 2016;9(1):64-69.
  14. Ottenhof SR, Djajadiningrat RS, Thygesen HH, Jakobs PJ, Józwiak K, Heeren AM, et al. The prognostic value of immune factors in the tumor microenvironment of penile squamous cell carcinoma. Front Immunol. 2018;9(1):1253.
  15. Gao W, Ye G, Liu L, Wei L. The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression. 2018;15(5):7661–7668.
  16. Bellmunt J, Mullane SA, Werner L, Fay AP, Callea M, Leow JJ, et al. Association of PD-L1 expression on tumor-in fi ltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol. 2015;26(4):812–817.
  17. Burger M, Catto JWF, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol [Internet]. 2013;63(2):234–241.
  18. Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. medical sciences Epidemiology of Bladder Cancer. Med Sci. 2020;8(15):1–12.
  19. Ibrahim D, Abdelbary E, Hegazy A. Evaluation of Fascin and Mmp-9 Expression As Markers of Invasion in Urothelial Carcinoma of the Urinary Bladder. Int J Adv Res. 2016;4(8):401–408.
  20. Guntarno NC, Rahaju AS, Kurniasari N. The Role of MMP-9 and VEGF in the Invasion State of Bladder Urothelial Carcinoma. Indones Biomed J. 2021;13(1):61–67.
  21. Wu GJ, Bao JS, Yue ZJ, Zeng FC, Cen S, Tang ZY, et al. Elevated expression of matrix metalloproteinase-9 is associated with bladder cancer pathogenesis. J Cancer Res Ther. 2018;14(8):54.
  22. Nechifor-Boilă IA, Loghin A, Nechifor-Boilă A, Decaussin-Petrucci M, Voidăzan S, Chibelean BC, et al. Pd-l1 expression in muscle invasive urothelial carcinomas as assessed via immunohistochemistry: Correlations with specific clinical and pathological features, with emphasis on prognosis after radical cystectomy. Life. 2021;11(5):1–12.
  23. Pierconti F, Raspollini MR, Martini M, Larocca LM, Bassi PF, Bientinesi R, et al. Correction to: PD-L1 expression in bladder primary in situ urothelial carcinoma: evaluation in BCG-unresponsive patients and BCG responders. Virchows Arch. 2020;477(2):327.
  24. Tsai MY, Chiang PC, Chen CH, Sung MT, Huang SC, Suen JL, et al. Comparison of the prognostic value of Ki-67 and programmed cell death ligand-1 in patients with upper tract urothelial carcinoma. J Clin Med. 2021;10(16):6–8.
  25. Lestari AAW, Prabawa IPY, Wiranata S, Supadmanaba IGP. High eosinophils lymphocyte ratio (ELR) related with subtype of breast cancer in Sanglah General Hospital, Bali. Annals of Oncology,. 2018;29(1):ix11-ix12.

How to Cite

Sumadi, I. W. J., Citra, D. ., & Artha, I. G. A. (2024). Ekspresi Matrix Metalloproteinase-9 (MMP-9) dan Programmed Death Ligand-1 (PD-L1) pada karsinoma urotelial kandung kemih dengan invasi otot lebih tinggi dibandingkan karsinoma urotelial kandung kemih tanpa invasi otot. Intisari Sains Medis, 15(1), 266–271.




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