Skip to main content Skip to main navigation menu Skip to site footer

Hubungan Lymph Vessel Density (LVD) dengan invasi limfatik dan metastasis kelenjar getah bening regional pada karsinoma payudara invasif tipe tidak spesifik di RSUP Sanglah, Bali, Indonesia

Abstract

Background: Lymph Node Metastasis (LNM) is considered the most important prognostic factor in breast cancer. The progress of lymphatic metastasis is thought to involve the proliferation of lymphatic vessels (lymphangiogenesis), Lymph Vessel Invasion (LVI), and lymph node metastasis step by step. This study aims to evaluate the association between LVD with LVI and regional LNM in invasive breast carcinoma of no special type.

Methods: This study used a cross-sectional analytical study, using a sample of 38 paraffin-embedded tissue from the patient with invasive breast carcinoma of no special type in Sanglah General Hospital, Bali, Indonesia, in 2018. The sample will be used to assess LVD and LVI by D2-40 immunohistochemistry. Expression of D2-40 with vigorous-intensity was evaluated on the membrane and cytoplasm of lymphatic endothelial cells to determine the definition of lymphatic vessels. Lymph vessel density was determined by counting the number of lumens of peritumoral lymphatic vessels in five fields of view with the densest lymphatic vessel lumen using a Leica microscope (DM750, 400x, area 0.225mm2). Data were analyzed using SPSS version 24 for Windows.

Results: The LVD cut-off value is 16.5 lymphatic vessel lumens/0.225 mm2 (65.4% for sensitivity and area Under the Curve (AUC)=70.2%). Then cases were classified into the category of high LVD (?16,5 lymphatic vessel lumen/0,225 mm2) and low LVD (<16.5 lymphatic vessels lumen/0,225 mm2). The study found a statistically significant association between LVD and lymph vessel invasion (PR=3.6; p=0.043; 95%CI=0.88-14.78) and regional lymph node metastases (PR =1.7; p=0.02; 95%CI=1.03-2.79).

Conclusion: This study proved an association between LVD with lymph vessel invasion and regional lymph node metastases. 

 

Latar Belakang: Metastasis Kelenjar Getah Bening (KGB) dianggap sebagai faktor prognostik yang paling penting pada kanker payudara. Perkembangan metastasis limfatik diduga melibatkan proliferasi pembuluh limfatik (limfangiogenesis), Lymph Vessel Invasion (LVI) atau invasi limfatik, dan metastasis kelenjar getah bening secara bertahap. Penelitian ini bertujuan untuk mengevaluasi hubungan antara Lymph Vessel Density (LVD) dengan invasi limfatik dan metastasis kelenjar getah bening regional pada karsinoma payudara invasif tipe tidak spesifik.

Metode: Penelitian ini menggunakan metode analitik potong lintang dengan sampel 38 blok parafin dari pasien karsinoma payudara invasif tipe tidak spesifik di RSUP Sanglah, Bali, Indonesia tahun 2018. Penilaian LVD dan LVI dengan pulasan imunohistokimia D2-40. Ekspresi D2-40 dengan intensitas yang kuat dievaluasi pada membran dan sitoplasma sel endotel limfatik untuk menetapkan definisi pembuluh limfatik. Lymph vessel density ditentukan dengan menghitung jumlah lumen pembuluh limfatik peritumoral pada lima lapangan pandang yang memiliki lumen pembuluh limfatik terpadat, menggunakan mikroskop Leica (DM750, 400x, luas area 0,225mm2). Data dianalisis dengan SPSS versi 24 untuk Windows.

Hasil: Nilai cut-off LVD adalah 16,5 lumen pembuluh limfatik/0,225 mm2 (sensitivitas 65,4% dan Area Under the Curve (AUC)=70,2%). Kemudian kasus dikategorikan menjadi LVD tinggi (?16,5 lumen pembuluh limfatik / 0,225 mm2) dan LVD rendah (<16,5 lumen pembuluh limfatik / 0,225 mm2). Hasil analisis statistik menunjukkan bahwa terdapat hubungan antara LVD dengan invasi limfatik (PR=3,6; p=0,043; IK 95%=0,88-14,78) dan metastasis KGB regional (PR=1,7; p=0,02; IK 95%=1,03-2,79).

Kesimpulan: Penelitian ini membuktikan bahwa terdapat hubungan antara LVD dengan invasi limfatik dan metastasis KGB regional. 

References

1. 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.
2. Paduch R. The role of lymphangiogenesis and angiogenesis in tumor metastasis. Cell Oncol (Dordr). 2016;39(5):397-410.
3. Ran S, Volk L, Hall K, Flister MJ. Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology. 2010;17(4):229-251.
4. Zhang S, Zhang D, Yi S, Gong M, Lu C, Cai Y, et al. The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis. Oncotarget. 2017;8(2):2863-2873.
5. Tammela T, Alitalo K. Lymphangiogenesis: Molecular mechanisms and future promise. Cell. 2010;140(4):460-476.
6. Andree C, Schmidt VJ, Munder BI, Seidenstücker K, Behrendt P, Witzel C, et al. Detecting of breast cancer metastasis by means of regional lymph node sampling during autologous breast reconstruction--a screening of 519 consecutive patients. Med Sci Monit. 2018;18(10):CR605-10.
7. Hermansyah, D, Albar ZA, Purwanto DJ, Sari L, Putri RL. CD 105 as prognostic factors in advanced stage breast cancer patients. Bali Medical Journal. 2017;6(1):227-235.
8. Widodo I, Ferronika P, Harijadi A, Triningsih FE, Utoro T, Soeripto. Clinicopathological significance of lymphangiogenesis and tumor lymphovascular invasion in indonesian breast cancers. Asian Pac J Cancer Prev. 2013;14(2):997-1001.
9. Kandemir NO, Barut F, Bektas S, Ozdamar SO. Can lymphatic vascular density be used in determining metastatic spreading potential of tumor in invasive ductal carcinomas?. Pathol Oncol Res. 2012;18(2):253-262.
10. Kanngurn S, Thongsuksai P, Chewatanakornkul S. Chalkley microvessel but not lymphatic vessel density correlates with axillary lymph node metastasis in primary breast cancers. Asian Pac J Cancer Prev. 2013;14(1):583-587.
11. Kumar A, Pandey V, Ansari MA, Srivastava V, Kumar M. Lymphangiogenesis as a Prognostic Marker in Breast Cancer Using D2-40 as Lymphatic Endothelial Marker–A Preliminary Study. European Journal of Cancer. 2012;45(5):S89.
12. Mohammed RA, Martin SG, Mahmmod AM, Macmillan RD, Green AR, Paish EC, et al. Objective assessment of lymphatic and blood vascular invasion in lymph node-negative breast carcinoma: findings from a large case series with long-term follow-up. J Pathol. 2011;223(3):358-65.
13. Tao Z, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast Cancer: Epidemiology and Etiology. Cell Biochem Biophys. 2015;72(2):333-338.
14. Fulga V, Rudico L, Balica AR, Cimpean AM, Saptefrati L, Raica M. Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile?. Pol J Pathol. 2015;66(1):30-37.
15. Momenimovahed Z, Salehiniya H. Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer (Dove Med Press). 2019;11:151-164.
16. Sumadi IWJ, Susraini AAAN. Tingkat Kesesuaian Diagnosis Invasi Limfatik pada Karsinoma Duktal Invasif Payudara pada Pulasan Hematoksilin-Eosin Dibandingkan dengan Pulasan Imunohistokimia VEGFR-3. Majalah Patologi Indonesia Indonesia. 2012;21(1):14-19.
17. Rahman M, Mohammed S. Breast cancer metastasis and the lymphatic system. Oncol Lett. 2015;10(3):1233-1239.
18. Guleria P, Srinivas V, Basannar D, Dutta V. Comparison of lymphangiogenesis, lymphatic invasion, and axillary lymph node metastasis in breast carcinoma. Indian J Pathol Microbiol. 2018;61(2):176-180.
19. Tseng HS, Chen LS, Kuo SJ, Chen ST, Wang YF, Chen DR. Tumor characteristics of breast cancer in predicting axillary lymph node metastasis. Med Sci Monit. 2014;20:1155-1161.
20. Karaman S, Detmar M. Mechanisms of lymphatic metastasis. J Clin Invest. 2014;124(3):922-928.
21. Widiana IK, Suryawisesa IB, Tirthayasa INW. The role of lymphatic and vascular invasion in lymph node metastasis in T1/T2N0 breast cancer patients at Sanglah General Hospital. Indian Journal of Scientific Research. 2016;7(1):45-53.
22. Sriwidyani NP, Manuaba IBTW, Alit-Artha IG, Mantik-Astawa IN. Tumor budding in breast carcinoma: relation to E-Cadherin, MMP-9 expression, and metastasis risk. Bali Medical Journal 2016;5(3):497-501.
23. Kos M, Lenicek T. Lymphatic and Small Blood Vessel Density in The Tumor and Peritumoral Tissue in Invasive Breast Carcinoma of No Special Type. Croation Journal of Oncology, 2018;46(1):5-13.
24. Zhao YC, Ni XJ, Li Y, Dai M, Yuan ZX, Zhu YY, et al. Peritumoral lymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients. World J Surg Oncol. 2012;10:165.

How to Cite

Simbolon, K. R., Dewi, I. G. A. S. M., Sriwidyani, N. P., Maker, L. P. I. I., Saputra, H., & Muliarta, I. M. (2021). Hubungan Lymph Vessel Density (LVD) dengan invasi limfatik dan metastasis kelenjar getah bening regional pada karsinoma payudara invasif tipe tidak spesifik di RSUP Sanglah, Bali, Indonesia. Intisari Sains Medis, 12(2), 606–612. https://doi.org/10.15562/ism.v12i2.1037

HTML
132

Total
151

Share

Search Panel

Katrin Rotua Simbolon
Google Scholar
Pubmed
ISM Journal


I Gusti Ayu Sri Mahendra Dewi
Google Scholar
Pubmed
ISM Journal


Ni Putu Sriwidyani
Google Scholar
Pubmed
ISM Journal


Luh Putu Iin Indrayani Maker
Google Scholar
Pubmed
ISM Journal


Herman Saputra
Google Scholar
Pubmed
ISM Journal


I Made Muliarta
Google Scholar
Pubmed
ISM Journal