Research Article

Hubungan antara ekspresi c-MET dengan derajat diferensiasi histologi dan tingkat kedalaman invasi pada infiltrating urothelial carcinoma kandung kemih di RSUP Sanglah, Bali, Indonesia

Kadek Agus Suhardinatha Putra , I Gusti Ayu Sri Mahendra Dewi, Herman Saputra, Ni Wayan Winarti, Anak Agung Ayu Ngurah Susraini, Ni Putu Ekawati, I Made Muliarta

Kadek Agus Suhardinatha Putra
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia. Email: agssuhardinatha@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

Ni Wayan Winarti
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 Ekawati
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia

I Made Muliarta
Departemen Fisiologi, Fakultas Kedokteran, Universitas Udayana, Bali Indonesia
Online First: July 31, 2021 | Cite this Article
Putra, K., Dewi, I., Saputra, H., Winarti, N., Susraini, A., Ekawati, N., Muliarta, I. 2021. Hubungan antara ekspresi c-MET dengan derajat diferensiasi histologi dan tingkat kedalaman invasi pada infiltrating urothelial carcinoma kandung kemih di RSUP Sanglah, Bali, Indonesia. Intisari Sains Medis 12(2): 513-518. DOI:10.15562/ism.v12i2.1022


Background: c-MET is a tyrosine kinase receptor that binds specifically to its ligand, namely hepatocyte growth factor (HGF). c-MET signaling deviations play a role in the progressivity of a wide variety of malignancies including bladder cancer. This study aims to determine the relationship between c-MET expression with the histological differentiation and depth of invasion in infiltrating urothelial carcinoma of bladder.

Methods: This study was a cross-sectional analytical study with 42 sample sizes. The samples were taken from a paraffin block of patients with infiltrating urothelial carcinoma of the bladder, that has performed resection and histopathological examination who were examined at the Anatomical Pathology Laboratory of Sanglah Hospital Denpasar from 2015-2020. The c-MET expression was examined by immunohistochemical staining of c-MET and evaluated using the H-score method. Data were analyzed using SPSS version 20 for Windows.

Results: Fisher's Exact test showed a statistically significant association between c-MET expression and the histological differentiation grade (p = 0.000). There was also a significant association between c-MET expression and depth of invasion with the Chi-Square test (p = 0.016), the Prevalence Ratio (PR) was 2.0 (95% CI = 1.2-3.6).

Conclusion: In conclusion, there is an association between c-MET expression with the histological differentiation grade and depth of invasion in the infiltrating urothelial carcinoma of bladder. High c-MET expression had twice the risk of developing advanced invasion.

 

Latar Belakang: c-MET merupakan reseptor tirosin kinase yang berikatan secara spesifik dengan ligannya, yaitu faktor pertumbuhan hepatosit (HGF). Penyimpangan c-MET signaling diketahui berperan dalam agresivitas berbagai macam keganasan termasuk kanker kandung kemih. Penelitian ini bertujuan untuk mengetahui hubungan antara ekspresi c-MET dengan derajat diferensiasi histologi dan tingkat kedalaman invasi pada infiltrating urothelial carcinoma kandung kemih.

Metode: Penelitian ini merupakan studi analitik potong lintang dengan besar sampel adalah 42, yang berasal dari blok parafin penderita infiltrating urothelial carcinoma kandung kemih yang diperiksa histopatologi di Laboratorium Patologi Anatomi RSUP Sanglah Denpasar dari 2015-2020. Ekspresi c-MET diperiksa dengan pengecatan imunohistokimia c-MET dan dievaluasi menggunakan metode H-score. Data dianalisis dengan SPSS versi 20 untuk Windows.

Hasil: Uji Fisher’s Exact menunjukkan hubungan yang bermakna secara statistik antara ekspresi c-MET dengan derajat diferensiasi histologi (p=0,000). Didapatkan juga hubungan yang bermakna antara ekspresi c-MET dengan tingkat kedalaman invasi dengan uji Chi-Square (p=0,016), prevalence ratio 2,0 (IK 95%=1,2-3,6).

Kesimpulan: Sebagai simpulan terdapat hubungan antara ekspresi c-MET dengan derajat diferensiasi histologi dan tingkat kedalaman invasi pada infiltrating urothelial carcinoma kandung kemih. Ekspresi c-MET tinggi memiliki risiko dua kali lebih besar mengalami invasi lanjut. c-MET diharapkan dapat menjadi faktor prognostik yang bermanfaat dalam penatalaksanaan infiltrating urothelial carcinoma kandung kemih.

References

Xu X, Zhang G, He L, Zhu Y. Clinicopathological impacts of c-Met overexpression in bladder cancer: evidence from 1,336 cases. Onco Targets Ther. 2019;12:2695-2702.

Miyazaki J, Nishiyama H. Epidemiology of urothelial carcinoma. Int J Urol. 2017;24(10):730-734.

Tabata M, Ikeda M, Urakami S, Takahashi S, Sakaguchi K, Kurosawa K, et al. Impact of adjuvant chemotherapy on patients with pathological Stage T3b and/or lymph node metastatic bladder cancer after radical cystectomy. Jpn J Clin Oncol. 2015;45(10):963-7.

Enokida H, Yoshino H, Matsushita R, Nakagawa M. The role of microRNAs in bladder cancer. Investig Clin Urol. 2016;57 Suppl 1(Suppl 1):S60-S76.

Zhang T, Boominathan R, Foulk B, Rao C, Kemeny G, Strickler JH, et al. Development of a Novel c-MET-Based CTC Detection Platform. Mol Cancer Res. 2016;14(6):539-547.

Kim YW, Yun SJ, Jeong P, Kim SK, Kim SY, Yan C, et al. The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease. PLoS One. 2015;10(7):e0134552.

Cheng HL, Trink B, Tzai TS, Liu HS, Chan SH, Ho CL, et al. Overexpression of c-met as a prognostic indicator for transitional cell carcinoma of the urinary bladder: a comparison with p53 nuclear accumulation. J Clin Oncol. 2002;20(6):1544-50.

Liu Y, Bui MM, Xu B. Urothelial Carcinoma With Squamous Differentiation Is Associated With High Tumor Stage and Pelvic Lymph-Node Metastasis. Cancer Control. 2017;24(1):78-82.

Al-Maghrabi J, Emam E, Gomaa W, Saggaf M, Buhmeida A, Al-Qahtani M, et al. c-MET immunostaining in colorectal carcinoma is associated with local disease recurrence. BMC Cancer. 2015;15:676.

Ho-Yen CM, Green AR, Rakha EA, Brentnall AR, Ellis IO, Kermorgant S, et al. C-Met in invasive breast cancer: is there a relationship with the basal-like subtype? Cancer. 2014;120(2):163-71.

Xu Y, Peng Z, Li Z, Lu M, Gao J, Li Y, et al. Expression and clinical significance of c-Met in advanced esophageal squamous cell carcinoma. BMC Cancer. 2015;15:6.

Chung KT. The etiology of bladder cancer and its prevention. J Cancer Sci Ther. 2013;5(10):346–61.

Umbas R, Safriadi F, Mochtar CA, Djatisoesanto W, Hamid AR. Urologic cancer in Indonesia. Jpn J Clin Oncol. 2015;45(8):708-712.

Pratiwi DA, Yudiana W, Oka AAG, Niryana W, Widyadharma IPE. Clinical and Pathological Characteristics of Bladder Cancer Patients at Sanglah General Hospital between January 2013 - December 2016. Int J Sci Res. 2018;7(2):845–847.

Cumberbatch MGK, Jubber I, Black PC, Esperto F, Figueroa JD, Kamat AM, et al. Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018. Eur Urol. 2018;74(6):784-795.

Wiranata S, Anjani IAW, Saputra IPGS, Sadvika IGAS, Prabawa IPY, Supadmanaba IG, et al. Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to- Lymphocyte Ratio as a Stage Determination in Breast Cancer. Open Access Macedonian Journal of Medical Sciences. 2020;8(B):1058-1063.

Türk H, Ün S, Ergani B. The Effect of Sex and Age Differences on Pathology Results in Primary Bladder Cancer Patients. Üroonkoloji Bülteni. 2017;16(3):81–85.

Miyata Y, Asai A, Mitsunari K, Matsuo T, Ohba K, Mochizuki Y, et al. Met in urological cancers. Cancers (Basel). 2014;6(4):2387-403.

Mukae Y, Miyata Y, Nakamura Y, Araki K, Otsubo A, Yuno T, et al. Pathological roles of c-Met in bladder cancer: Association with cyclooxygenase-2, heme oxygenase-1, vascular endothelial growth factor-A and programmed death ligand 1. Oncol Lett. 2020;20(1):135-144.

Moosavi F, Giovannetti E, Saso L, Firuzi O. HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers. Crit Rev Clin Lab Sci. 2019;56(8):533-566.


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