Meme kanseri hastalarında vasküler endotelyal büyüme faktörü-C ve lenf nodu metastazı ilişkisi

Year 2019, Volume: 3 Issue: 2, 124 - 127, 25.02.2019

İbrahim Mungan , Osman Doğru Erhan Aygen Adile Ferda Dağlı

https://doi.org/10.28982/josam.443836

Abstract

Giriş: Meme kanseri (MK) dünya çapında en sık görülen 2. kanserdir ve vakaların çoğu sporadiktir. MK yayılım için esas olarak lenfatik sistemi seçer ve aksiller lenf düğümleri (LN) sıklıkla bu yayılımda rol alır. Lenf nodu metastazı (LNM), tümör kaynaklı lenfanjiyojenik büyüme faktörleri, özellikle vasküler endotelyal büyüme faktörü (VEGF) ailesi tarafından yönlendirilir. MK vakalarında daha yüksek oranda serum VEGF-C düzeyleri tespit edilmiştir.Bu çalışmada, tümör örneklerinde VEGF-C ekspresyon paternini ve immünohistokimyasal olarak LNM ile VEGF-C ekspresyonunun ilişkisini araştırmayı amaçladık.

Yöntemler: Bu klinik çalışmada, Nisan 2006 ile Mart 2007 arasında cerrahi tedavi alan primer invaziv duktal meme kanserli 22 kadın hastadan Parafine gömülü örnekler alındı. MK doku kesitleri VEGF-C antikoru ile boyandı ve boyanma şiddeti ve yoğunluğuna göre değerlendirildi. İstatistiksel analiz, Windows için SPSS 15.0 sürümü kullanılarak gerçekleştirildi. Tüm analizlerde, 0.05'ten küçük bir ‘p’ değeri istatistiksel olarak anlamlı kabul edildi ve karşılaştırmalar 2 yönlü olarak yapıldı.

Bulgular: Tanı anında ortalama yaş 50 idi (dağılım: 24-82 yıl). Bu çalışmada, SI ve SS VEGF-C ekspresyonu temelinde LNM ile istatistiksel olarak anlamlı bir ilişki bulunmazken, hesaplanan IRS - değişken olarak LNM ile ilişkili gözlenmiştir. Tümör derecesi ise ne VEGF-C ekspresyonu ne de lenf nodu metastazı ile belirgin ilişkili gözlenmemiştir (p> 0,05).

Sonuç: VEGF-C IRS skoru ve aksiller lenf nodu düzeyi ile ilgileşiminin istatistiksel olarak anlamlı olduğu dikkati çekmektedir. Bu çalışmada, MK hastalarının tümöral örneklerinde LNM ile VEGF-C ilişkisini IHC boyaması ile gösterdik.

Keywords

Vasküler endotelyal büyüme faktörü –C, Lenf nodu metastazı, Meme kanseri

The relations of vascular endothelial growth factor–C and lymph node metastasis in breast cancer patients

Abstract

Aim: Breast cancer (BC) is the 2nd most common cancer worldwide and most of the cases are sporadic. BC chooses mainly the lymphatic system and axillary lymph nodes (LN) are frequently involved. Lymph node metastasis (LNM) is driven by tumor-derived lymphangiogenic growth factors, especially vascular endothelial growth factor (VEGF) family. Higher serum levels of VEGF-C have been detected in cases of BC. In the present study, we aim to investigate the expression pattern of VEGF-C in tumor specimens and the relation of VEGF-C expression with LNM by immunohistochemistry.

Methods: In this clinical, cross-sectional study, paraffin-embedded specimens were obtained from 16 female patients who had primary invasive ductal breast cancer and received surgical treatment between April 2006 and March 2007. BC tissue sections were stained with VEGF-C antibody and evaluated according to the severity and intensity of the staining. Statistical analysis was performed using SPSS version 15.0 for Windows and in all analyses, a ‘p’ value less than 0.05 was considered statistically significant and comparisons were 2-tailed.

Results: The average age at the time of diagnosis was 50 years (range: 24-82 years). In the present study, on the basis of SI and SS VEGF-C expression did not show statistically significant correlation with LNM, while calculated IRS - as a variable- was correlated with LNM. The grade of the tumor correlated neither with the VEGF-C expression nor with lymph node metastasis (p>0.05).

Conclusions: It is interesting that the correlation with VEGF-C IRS score and axillary lymph node level was found significant statistically. In the current study, we demonstrated the VEGF-C relation with LNM via IHC staining in tumoral samples of BC patients.

Keywords

Vascular endothelial growth factor–C, Lymph node metastasis, Breast cancer

References

• 1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86. doi: 10.1002/ijc.29210.
• 2. Raica M, Cimpean AM, Ceausu R, Ribatti D. Lymphatic microvessel density, VEGF-C, and VEGFR-3 expression in different molecular types of breast cancer. Anticancer Res. 2011;31:1757–64.
• 3. Wu QW, She HQ, Liang J, et al. Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer. BMC Cancer. 2012;12:47.
• 4. Zhang B-N, Cao X-C, Chen J-Y, et al. Guidelines on the diagnosis and treatment of breast cancer (2011 edition).Gland Surgery. 2012;1(1):39-61. doi:10.3978/j.issn.2227-684X.2012.04.07.
• 5. Zhang Y, Liu J, Lin J, et al. The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer. Oncotarget. 2016;7:9859–75. https://doi.org/10.18632/oncotarget.7126.
• 6. Wang CA, Tsai SJ. The non-canonical role of vascular endothelial growth factor-C axis in cancer progression. Exp Biol Med (Maywood). 2015;240(6):718–24. doi:10.1177/1535370215583802
• 7. Wang CA, Harrell JC, Iwanaga R, et al. Vascular endothelial growth factor C promotes breast cancer progression via a novel antioxidant mechanism that involves regulation of superoxide dismutase 3. Breast Cancer Res. 2014;16:462. doi: 10.1186/s13058-014-0462-2.
• 8. Zhao Y-C, Ni X-J, Li Y, et al. Peritumoral lymphangiogenesis induced by vascular endothelial growth factor C and D promotes lymph node metastasis in breast cancer patients. World Journal of Surgical Oncology. 2012;10:165. doi:10.1186/1477-7819-10-165.
• 9. Fakhrejahani E, Toi M. Antiangiogenesis therapy for breast cancer: an update and perspectives from clinical trials. Jpn J Clin Oncol. 2014;44(3):197–207. doi:10.1093/jjco/hyt201
• 10. Liang B, Li Y. Prognostic Significance of VEGF-C Expression in Patients with Breast Cancer: A Meta-Analysis. Iranian Journal of Public Health. 2014;43(2):128-35.
• 11. Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001;7:192–8. doi: 10.1038/84643.
• 12. Nakamura Y, Yasuoka H, Tsujimoto M, et al. Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long-term follow-up. Mod Pathol. 2003;16(4):309-14.
• 13. Zhang XH, Huang DP, Guo GL, et al. Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer. BMC Cancer. 2008;8:4.
• 14. Zhang Z, Luo G, Tang H, et al. Prognostic significance of high VEGF-C expression for patients with breast cancer: An update meta analysis. PLoS One. 2016;11:e0165725. doi: 10.1371/journal.pone.0165725.
• 15. Schoppmann SF, Tamandl D, Roberts L, et al. HER2/neu expression correlates with vascular endothelial growth factor-C and lymphangiogenesis in lymph node-positive breast cancer. Ann Oncol. 2010;21:955–60.