A new approach to lymphedema following breast cancer treatment with lymphatic endothelial cell markers

Year 2021, , 322 - 328, 21.05.2021

Nilhan Nurlu , Gül Tuğba Bulut

https://doi.org/10.32322/jhsm.902393

Abstract

Amaç: Lenfödem (LE), aksiller lenf nodu diseksiyonu ve radyoterapi ile tedavi edilen meme kanserli olgularda yaygın gelişen iyatrojenik bir komplikasyondur. Bu çalışmada lenfödemli hastalarda meme kanseri tedavisi sonrası, lenfatik sistem endotelinden salınan, homeobox transkripsiyon faktörü (Prox-1), lenfatik damar endotel reseptörü-1 (LVYE-1) ve podoplanin (PDPN) belirteçlerinin serum düzeylerini araştırmayı amaçladık.
Metod: Çalışmanın LE grubunu meme kanseri tedavisi sonrası üst ekstremitede LE gelişen toplam 44 kadın hasta, kontrol grubunu ise demografik açıdan LE grubu ile benzer özellikler gösteren 44 sağlıklı kadın oluşturdu. Hastaların kol çevreleri ölçüldü ve her iki kol çevresi toplamları arasındaki fark (DSOAC) 2 cm veya ≥ %10 ise LE olarak kabul edildi. Serum Prox-1, LVYE-1 ve PDPN konsantrasyonları ticari ELISA (Enzyme-linked immunosorbent assay) ile ölçüldü.
Bulgular: LE grubunda Prox-1, LVYE-1 ve PDPN seviyeleri kontrol grubuna göre anlamlı olarak düşük bulundu (sırasıyla; p < 0.01, p = 0.02, p = 0.04). Prox-1 seviyeleri Evre 1 LE'li hastalarda Evre 2 LE’li hastalara göre anlamlı yüksekti (p<0.001). Prox-1 seviyeleri ile DSOAC ve çıkarılan aksiller lenf nodu sayısı arasında zayıf ve negatif korelasyon gözlemlenirken (r = −0.417 ve −0.426, sırasıyla; p < 0.01), DSOAC ve çıkarılan aksiller lenf nodu sayısı arasında orta derecede pozitif korelasyon saptandı (r = 0.533, p < 0.001).
Sonuç: Çalışmamız sonucunda meme kanseri tedavisine sekonder gelişen lenfödemde Prox-1, LVYE-1 ve PDPN seviyeleri düşük bulunmuştur. Lenfatik endotel hücre belirteçlerinin lenfödem ile ilişkisinin inceleneceği ileri araştırmalar, LE tanı, prognoz ve tedavisinde yeni perspektiflerin geliştirilmesine yardımcı olabilir.
Anahtar Kelimeler:Lenfatik endotel hücre belirteçleri, seconder lenfödem, lenfanjiogenez

Keywords

Lymphatic endothelial cell markers, secondary lymphedema, lymphangiogenesis

References

• Warren AG, Brorson H, Borud LJ, Slavin SA. Lymphedema: a comprehensive review. Ann Plast Surg 2007; 59: 464-72.
• Dayan JH, Ly CL, Kataru RP, Mehrara BJ. Lymphedema: pathogenesis and novel therapies. Annu Rev Med 2018; 69: 263-76.
• Grada AA, Phillips TJ. Lymphedema pathophysiology and clinical manifestations. J Am Acad Dermatol 2017; 77: 1009-20.
• Cormier JN, Askew RL, Mungovan KS, Xing Y, Ross MI, Armer JM. Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema. Cancer 2010; 116: 5138-49.
• Schunemann H, Willich N. Lymphedema after breast carcinoma: a study of 5868 cases. Dtsch Med Wochenschr 1997; 122: 536-41.
• Petrek JA, Senie RT, Peters M, Rosen PP. Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis. Cancer 2001; 92: 1368-77.
• Hinrichs CS, Watroba NL, Rezaishiraz H, et al. Lymphedema secondary to postmastectomy radiation: incidence and risk factors. Ann Surg Oncol 2004; 11: 573-80.
• Lasinski BB. Complete decongestive therapy for treatment of lymphedema. Semin Oncol Nurs 2013; 29: 20-7.
• Gerli R, Solito R, Weber E, Aglianó M. Specific adhesion molecules bind anchoring filaments and endothelial cells in human skin initial lymphatics. Lymphology 2000; 33: 148-57.
• Jurisic G, Detmar M. Lymphatic endothelium in health and disease. Cell Tissue Res 2009; 335: 97-108.
• Adamczyk LA, Gordon K, Kholová I, et al. Lymph vessels: the forgotten second circulation in health and disease. Virchows Arch 2016; 469: 3-17.
• Breslin JW, Kurtz KM. Lymphatic endothelial cells adapt their barrier function in response to changes in shear stress. Lymphat Res Biol 2009; 7: 22-37.
• Miteva DO, Rutkowski JM, Dixon JB, Kilarski W, Shields JD, Schwartz MA. Transmural flow modulates cell and fluid transport functions of lymphatic endothelium. Circ Res 2010; 106: 920-31.
• Ji RC. Lymphatic endothelial cells, lymphedematous lymphangiogenesis, and molecular control of edema formation. Lymphat Res Biol 2008; 6: 123-37.
• Wang S, Nie D, Rubin JP, Kokai L. Lymphatic endothelial cells under mechanical stress: altered expression of inflammatory cytokines and fibrosis. Lymphat Res Biol 2017; 15: 130-5.
• Kato S, Shimoda H, Ji RC, Miura M. Lymphangiogenesis and expression of specific molecules as lymphatic endothelial cell markers. Anat Sci Int 2006; 81: 71-83.
• Liersch R, Biermann C, Mesters RM, Berdel WE. Lymphangiogenesis in cancer: current perspectives. Recent Results Cancer Res 2010; 180: 115-35.
• Pan Y, Wang WD, Yago T. Transcriptional regulation of podoplanin expression by Prox1 in lymphatic endothelial cells. Microvasc Res 2014; 94: 96-102.
• Coriddi M, Khansa I, Stephens J, Miller M, Boehmler J, Tiwari P. Analysis of factors contributing to severity of breast cancer-related lymphedema. Ann Plast Surg 2015; 74: 22-5.
• Leung G, Baggott C, West C, et al. Cytokine candidate genes predict the development of secondary lymphedema following breast cancer surgery. Lymphat Res Biol 2014; 12: 10-22.
• Hayes S, Cornish B, Newman B. Comparison of methods to diagnose lymphoedema among breast cancer survivors: 6-month follow-up. Breast Cancer Res Treat 2005; 89: 221-26.
• Choi YH, Seo KS. Correlation among bioimpedance analysis, sonographic and circumferential measurement in assessment of breast cancer-related arm lymphedema. Lymphology 2014; 47: 123-33.
• McLaughlin SA, Wright MJ, Morris KT, et al. Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: Patient perceptions and precautionary behaviors. J Clin Oncol 2008; 26: 5213-19.
• Bernas MJ, Witte CL, Witte MH. The diagnosis and treatment of peripheral lymphedema: draft revision of the 1995 Consensus Document of the International Society of Lymphology Executive Committee for discussion at the September 3–7, 2001, XVIII International Congress of Lymphology in Genoa, Italy. Lymphology 2001; 34: 84-91.
• Miaskowski C, Dodd M, Paul SM, et al. Lymphatic and angiogenic candidate genes predict the development of secondary lymphedema following breast cancer surgery. PLoS One 2013; 8: e60164.
• Hadizadeh M, Mohaddes Ardebili SM, Salehi M, et al. GJA4/Connexin 37 Mutations correlate with secondary lymphedema following surgery in breast cancer patients. Biomedicines 2018; 6: 23.
• Larson D, Weinstein M, Goldberg I, et al. Edema of the arm as a function of the extent of axillary surgery in patients with stage I–II carcinoma of the breast treated with primary radiotherapy. Int J Radiat Oncol Biol Phys 1986; 12: 1575-82.
• Silberman H. Axillary lymphadenectomy for breast cancer: impact on survival. In: Silberman H, Silberman AW (ed) Surgical oncology: multidisciplinary approach to difficult problems. London: Arnold, 2002, pp 369-85.
• Ly CL, Kataru RP, Mehrara BJ. Inflammatory manifestations of lymphedema. Int J Mol Sci 2017; 18: 171.
• Shin K, Kataru RP, Park HJ, et al. Th2 cells and their cytokines regulate formation and function of lymphatic vessels. Nat Commun 2015; 6: 6196.
• Korybalska K, Luczak J, Swora-Cwynar E, et al. Weight loss-dependent and-independent effects of moderate calorie restriction on endothelial cell markers in obesity. J Physiol Pharmacol 2017; 68: 597-608.
• Hespe GE, Kataru RP, Savetsky IL, et al. Exercise training improves obesity-related lymphatic dysfunction. J Physiol 2016; 594: 4267-82.