Research Article

Hubungan antara ekspresi BRAF V600E dengan metastasis dan derajat diferensiasi pada adenokarsinoma kolorektal

Ni Kadek Ayu Maya Damayanti , Ni Wayan Winarti, Ni Putu Sriwidyani, Luh Putu Iin Indrayani Maker, Herman Saputra, I Made Muliarta

Ni Kadek Ayu Maya Damayanti
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia. Email: maydyanti3690@gmail.com

Ni Wayan Winarti
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

Luh Putu Iin Indrayani Maker
Departemen Patologi Anatomi, Fakultas Kedokteran, Universitas Udayana, RSUP Sanglah, Bali, Indonesia

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

I Made Muliarta
Departemen Fisiologi, Fakultas Kedokteran, Universitas Udayana, Bali, Indonesia
Online First: August 02, 2021 | Cite this Article
Damayanti, N., Winarti, N., Sriwidyani, N., Maker, L., Saputra, H., Muliarta, I. 2021. Hubungan antara ekspresi BRAF V600E dengan metastasis dan derajat diferensiasi pada adenokarsinoma kolorektal. Intisari Sains Medis 12(2): 524-529. DOI:10.15562/ism.v12i2.1045


Background: Colorectal carcinoma is a malignant epithelial tumor of the large bowel that occurs due to extrinsic and intrinsic factors. BRAF V600E gene mutation was found in about 10-15% of colorectal carcinoma. This mutation was associated with aggressive biologic behaviors, metastasis and lesser responsiveness to EGFR inhibitors therapy. This study aims to determine the association between BRAF V600E expression with metastasis and the degree of differentiation of colorectal adenocarcinoma.

Methods: This cross sectional study involved 43 samples of adenocarcinoma colorectal patients who had histopathological examinations in the period 2018-2019. Immunohistochemical were performed to assess the expression of BRAF V600E. This expression was concluded positively if 75% or more tumor cells showed intense cytoplasmic staining. Data were analyzed using SPSS version 20 for Windows.

Results: Within 43 colorectal adenocarcinoma cases, it was found 7 cases (16.3%) had a positive expression of BRAF V600E. This expression was found in metastasis cases (7/25), not found in cases without metastasis (0/18). There was an association between BRAF V600E expression and metastasis (p=0.014). The positive expressions of BRAF V600E were only found in low-grade differentiation (7/35 cases), were not found in high-grade differentiation (0/8 cases), and no association between BRAF V600E mutation and the degree of differentiation (p=0.167).

Conclusion: There was an association between BRAF V600E expression and metastasis of colorectal adenocarcinoma. There was no significant association between BRAF V600E expression and the degree of differentiation of colorectal adenocarcinoma.

 

Latar Belakang: Karsinoma kolorektal merupakan suatu tumor ganas epitelial usus besar yang terjadi akibat pengaruh dari faktor ekstrinsik dan intrinsik. Mutasi gen BRAF V600E ditemukan pada sekitar 10-15% kasus karsinoma kolorektal. Mutasi ini berkaitan dengan perilaku biologik agresif, metastasis, serta kurangnya respon terhadap terapi dengan inhibitor EGFR. Penelitian ini bertujuan untuk mengetahui adanya hubungan antara ekspresi BRAF V600E dengan metastasis dan derajat diferensiasi adenokarsinoma kolorektal.

Metode: Penelitian menggunakan rancangan analitik potong lintang dengan 43 sampel penderita adenokarsinoma kolorektal yang telah dilakukan pemeriksaan histopatologi pada periode tahun 2018-2019. Pulasan imunohistokimia dikerjakan untuk menilai ekspresi BRAF V600E. Ekspresi BRAF V600E dinyatakan positif jika 75% atau lebih sel tumor mununjukkan pulasan sitoplasma dengan intensitas kuat. Data dianalisis dengan SPSS versi 20 untuk Windows.

Hasil: Dari 43 kasus, ditemukan 7 kasus (16,3%) dengan ekspresi BRAF V600E positif. Ekspresi ini hanya dijumpai pada kasus dengan metastasis (7 dari 25 kasus), tidak dijumpai pada kasus tanpa metastasis (0 dari 18 kasus). Didapatkan hubungan bermakna antara ekspresi BRAF V600E dengan metastasis (p=0,014). Ekspresi BRAF V600E positif hanya ditemukan pada kasus derajat diferensiasi rendah (7 dari 35 kasus), tidak ditemukan pada derajat tinggi (0 dari 8 kasus), dan hubungan tersebut tidak bermakna secara statistik (p=0,167).

Kesimpulan: Terdapat hubungan antara ekspresi BRAF V600E dengan metastasis pada adenokarsinoma kolorektal. Tidak terdapat hubungan antara ekspresi BRAF V600E dengan derajat diferensiasi pada adenokarsinoma kolorektal.

References

Fredericks E, Dealtry G, Roux S. Molecular aspects of Colorectal Carcinogenesis: A Review. J Cancer Biol Re. 2015;3(1):1057.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90.

Caputo F, Santini C, Bardasi C, Cerma K, Casadei-Gardini A, Spallanzani A, et al. BRAF-Mutated Colorectal Cancer: Clinical and Molecular Insights. Int J Mol Sci. 2019;20(21):5369.

Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177-193.

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 Maced J Med Sci. 2020;8(B):1058-1063.

Luu LJ, Price TJ. BRAF mutation and its importance in colorectal cancer. Intech Open. 2019:1-18.

Ritterhouse LL, Barletta JA. BRAF V600E mutation-specific antibody: A review. Semin Diagn Pathol. 2015;32(5):400-408.

Loupakis F, Intini R, Cremolini C, Orlandi A, Sartore-Bianchi A, Pietrantonio F, et al. A validated prognostic classifier for V600EBRAF-mutated metastatic colorectal cancer: the 'BRAF BeCool' study. Eur J Cancer. 2019;118:121-130.

Zhang X, Wu J, Wang L, Zhao H, Li H, Duan Y, et al. HER2 and BRAFmutation in colorectal cancer patients: a retrospective study in Eastern China. PeerJ. 2020;8:e8602.

Wang X, Wei Q, Gao J, Li J, Li J, Gong J, et al. Clinicopathologic features and treatment efficacy of Chinese patients with BRAF-mutated metastatic colorectal cancer: a retrospective observational study. Chin J Cancer. 2017;36(1):81.

Manne U, Shanmugam C, Katkoori VR, Bumpers HL, Grizzle WE. Development and progression of colorectal neoplasia. Cancer Biomark. 2010;9(1-6):235-265.

Clarke CN, Kopetz ES. BRAF mutant colorectal cancer as a distinct subset of colorectal cancer: clinical characteristics, clinical behavior, and response to targeted therapies. J Gastrointest Oncol. 2015;6(6):660-667.

Dean TM. Carcinoma of the colon and rectum. A perspective for practicing physicians, with recommendations for screening. West J Med. 1977;126(6):431-440.

Fleming M, Ravula S, Tatishchev SF, Wang HL. Colorectal carcinoma: Pathologic aspects. J Gastrointest Oncol. 2012;3(3):153-173.

Marzouk O, Schofield J. Review of histopathological and molecular prognostic features in colorectal cancer. Cancers (Basel). 2011;3(2):2767-2810.

Toon CW, Walsh MD, Chou A, Capper D, Clarkson A, Sioson L, et al. BRAFV600E immunohistochemistry facilitates universal screening of colorectal cancers for Lynch syndrome. Am J Surg Pathol. 2013;37(10):1592-1602.

Kwon JH, Jeong BK, Yoon YS, Yu CS, Kim J. Utility of BRAF VE1 Immunohistochemistry as a Screening Tool for Colorectal Cancer Harboring BRAF V600E Mutation. J Pathol Transl Med. 2018;52(3):157-163.

Haraldsdottir S, Einarsdottir HM, Smaradottir A, Gunnlaugsson A, Halfdanarson TR. Colorectal cancer - review. Laeknabladid. 2014;100(2):75-82.

Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89-103.

Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145-164.

Wong MC, Ding H, Wang J, Chan PS, Huang J. Prevalence and risk factors of colorectal cancer in Asia. Intest Res. 2019;17(3):317-329.

Putranto AS, Julistian J. Risk Factors of Colorectal Carcinoma Incidence in Young Adults: A Meta-analysis. The New Ropanasuri Journal of Surgery. 2019;4(1):1–6.

Dewi NNA, Sumadi IWJ, Sun HS. Molecular Profile of Colorectal Cancer Patients in Bali Based On Methylation Of O6-Methylguanine DNA Methyltransferase Promoter Region and Mutation of BRAF and Kirsten Rat Sarcoma Viral Oncogene Homolog Gene. J Med Sci. 2020;20(10):1-8.

Hernowo BS, Ariyanni F, Suryanti S, Hassan AH. Use of BRAF V600E as a molecular marker in aggressive colorectal cancer. Acta Med Indones. 2014;46(2):104-110.

Wang J, Shen J, Huang C, Cao M, Shen L. Clinicopathological Significance of BRAFV600E Mutation in Colorectal Cancer: An Updated Meta-Analysis. J Cancer. 2019;10(10):2332-2341.

Vilkin A, Niv Y, Nagasaka T, Morgenstern S, Levi Z, Fireman Z, et al. Microsatellite instability, MLH1 promoter methylation, and BRAF mutation analysis in sporadic colorectal cancers of different ethnic groups in Israel. Cancer. 2009;115(4):760-9.

Rako I, Jakic-Razumovic J, Katalinic D, Sertic J, Plestina S. Mutation pattern of KRAS and BRAF oncogenes in colorectal cancer patients. Neoplasma. 2012;59(4):376-383.

Saridaki Z, Tzardi M, Sfakianaki M, Papadaki C, Voutsina A, Kalykaki A, et al. BRAFV600E mutation analysis in patients with metastatic colorectal cancer (mCRC) in daily clinical practice: correlations with clinical characteristics, and its impact on patients' outcome. PLoS One. 2013;8(12):e84604.

Inamura K. Colorectal Cancers: An Update on Their Molecular Pathology. Cancers (Basel). 2018;10(1):26.

Minhajat R, Benyamin AF, Miskad UA. The Relationship Between Histopathological Grading and Metastasis in Colorectal Carcinoma Patients. 2020;5(2):51–60.


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