Evaluation of serum matrix metalloproteinase 2-7-9, tissue matrix metalloproteinase inhibitor 1, vascular endothelial growth factor, interleukin 6 and interleukin 8 levels in breast cancinoma

Yıl 2019, Cilt: 12 Sayı: 2, 261 - 267, 28.05.2019

Serkan Değirmencioğlu , Aydın Demiray , Atike gökçen Demiray , Burcu Taskoylu Gamze gököz Doğu

https://doi.org/10.31362/patd.491863

Öz

Purpose: The
raising incidence of breast cancer and development of treatment modalities
cause prolongation of survival and new markers are needed for follow up. Serum
matrix metalloproteinase 2, 7, 9 (MMP2, MMP7, MMP9), tissue matrix
metalloproteinase inhibitor 1 (TIMP1), interleukin 6, interleukin 8 and
vasculer endotelial growth factor (VEGF) take different parts on
cancerogenesis. The aim of study is to evaluate the relationship between these
markers and clinical stage, histopathologic features and laboratuary parameters.

Materials
and methods: Seventyeight pathologically proven,
chemotherapy naive breast cancer patients were enrolled. The analyses were
carried out using SPSS v15 and p<0.05 was accepted as significant.
Descriptive studies were analyzed using chi-square test and Mann-Whitney U-test
depending on group numbers.

Results: The
median age of patients were 52±11.6. Patients were divided to non-metastatic
and metastatic pattern. VEGF values were 3.4 fold higher in metastatic group.
Raising of CA15-3 levels were statistically correlated with MMP9 and IL6. The
elevation of LDH were associated with raised VEGF and TIMP1. CRP elevation was
correlated with increased IL8, IL6 and MMP9. Raising of VEGF was associated
with progression. VEGF levels of patients lost in follow up were higher
although there was no statistically significance. MMP7 levels were lower in
hormon positive group than negative group. MMP2 levels were higher in HER2 (3+)
group than HER2 (0/1+/2+) patient group. 
TIMP1 levels were lower in patients whom ki 67 ratios were above 40%
than below 40%.

Conclusion: This
is a preliminary study with low patient number and short follow up time.

Anahtar Kelimeler

Breast cancer, VEGF, IL6, IL8

Meme kanserinde serum matriks metalloproteinaz 2-7-9, doku matriks metalloproteinaz inhibitörü 1, vasküler endotelial büyüme faktörü, interlökin 6 ve interlökin 8 düzeylerinin değerlendirilmesi

Öz

Amaç:
Meme kanseri insidansının artması ve
gelişen tedaviler ile sağkalımın uzaması izlemde yeni belirteçlere gereksinim
ortaya çıkarmaktadır. Serum matriks metalloproteinaz 2, 7, 9 (MMP2, MMP7, MMP9),
doku matriks metalloproteinaz inhibitörü1 (TIMP1), interlökin 6, interlökin 8
ve vasküler endoteliyal büyüme faktörü (VEGF) kanserogenezin farklı basamaklarında
rol almaktadırlar. Çalışmamızın amacı meme kanseri hastalarında bu
parametrelerin klinik evre, histopatolojik özellikler ve laboratuar değerleri
üzerine etkilerini değerlendirmektir.

Gereç
ve Yöntem: Meme kanseri patolojik
tanısı konmuş kemoterapi naif yetmiş sekiz kadın hasta çalışmaya alındı. İstatistik,
Statistical Package for Social Sciences version15 ile hesaplandı. Sonuçlar %95
güven aralığında değerlendirildi. p<0,05 olması istatistiksel olarak anlamlı
kabul edildi. Hasta gruplarını karşılaştırmalarında ki-kare ve Mann Whitney-U
testi uygulandı.

Bulgular:
Hastaların medyan yaşı 52±11,6
bulundu. Hastalar “non-metastatik” ve “metastatik” şeklinde iki gruba ayrıldı.
Metastatik grupta serum VEGF değeri 3,4 kat yüksek saptandı. Serum CA15-3 seviyesinde
yükselme, artmış MMP9 ve IL6 seviyeleri ile anlamlı ilişkiliydi. Serum LDH
seviyesi artmış hastalarda serum VEGF ve TIMP1 seviyeleri anlamlı arttı. Serum
CRP artışı IL8, IL6 ve MMP9 artışı ile ilişkili bulundu. Serum VEGF seviyeleri
progrese olgularda yüksekti. İzlemde kaybedilen hastaların serum VEGF seviyesi
daha yüksek olmakla beraber istatistiksel anlamlı değildi. Hormon pozitif
grupta negatif gruba göre serum MMP7 seviyeleri anlamlı düşük saptandı. HER2
(3+) hasta grubunda serum MMP2 seviyeleri HER2 (0/1+/2+) hasta grubuna göre
daha yüksekti. Serum TIMP1 seviyesi ki 67 oranı %40 ve üzeri hastalarda, oran
%40 altında olan hastalara göre anlamlı düşük bulundu.

Sonuç: Çalışmamız kısıtlı hasta sayısı ile yapılan kısa
takip süresine sahip bir ön çalışma özelliğindedir.

Anahtar Kelimeler

Meme kanseri, VEGF, IL6, IL8

Kaynakça

• 1)Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.
• 2) Shim KN, Jung SA, Joo YH, Yoo K. Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer. J Gastroenterol 2007;42:120-128.
• 3) Curran S, Murray GI. Matrix metalloproteinase in tumour invasion and metastasis. J Pathol 1999;189:300-308.
• 4) Monig SP, Baldus SE, Hennecken JK, et al. Expression of MMP-2 is associated with progression and lymph node metastasis of gastric carcinoma. Histopathology 2001;39:597-602.
• 5) Passlick B, Sienel W, Seen-Hibler R, et al.Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early-stage non-small cell lung cancer. Clin Cancer Res 2000;6:3944-3948.
• 6) Pyke C, Ralfkiaer E, Tryggvason K, Dano K. Messenger RNA for two type IV collagenase is located in stromal cells in human colon cancer. Am J Pathol 1993;142:359-365.
• 7) Stetler-Stevenson WG, Krutzsch HC, Liotta LA. Tissue inhibitors of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family. J Biol Chem 1989;264:17374-17378.
• 8) Parsons SL, Watson SA, Brown PD, Collins HM, Steele RJ. Matrix metalloproteinases. Br J Surg 1997;84:160-166.
• 9) Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002;295:2387-2392.
• 10) Zeng ZS, Cohen AM, Zhang ZF, Stetler-Stevenson W, Guillem JG. Elevated tissue inhibitor of metalloproteinase 1 RNA in colorectal cancer stroma correlates with lymph node and distant metastases. Clin Cancer Res 1995;1:899-906.
• 11)Dethlefsen C, Hojfeldt G, Hojman P. The role of intratumoral and systemic IL-6 in breast cancer. Breast Cancer Res Treat 2013;138(3):657–664.
• 12)Todorovic-Rakovic N, Milovanovic J. Interleukin-8 in breast cancer progression. J Interf Cytokine Res 2013;33(10):563–570.
• 13) Ma Y, Ren Y, Dai ZJ, Wu CJ, Ji YH, Xu J. IL-6, IL-8 and TNF-alpha levels correlate with disease stage in breast cancer patients. Adv Clin Exp Med 2017;26(3):421–426.
• 14) Bachelot T, Ray-Coquard I, Menetrier-Caux C, Rastkha M, Duc A, Blay JY. Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients, Brit J Cancer 2003;88(11):1721–1726.
• 15) Li S, Wang L, Meng Y, Chang Y, Xu J, Zhang Q. Increased levels of LAPTM4B, VEGF and survivin are correlated with tumor progression and poor prognosis in breast cancer patients. Oncotarget 2017;8:41282–41293.
• 16) Zhang M, Teng X, Guo X, Li Z, Han J, Yao L. Expression of tissue levels of matrix metalloproteinases and their inhibitors in breast cancer. The Breast 2013;22:330-334.
• 17) Jian WG, Davies G, Martin TA, et al. Targeting matrilysin and its impact on tumor growth in vivo: the potential implications in breast cancer therapy. Clin Cancer Res 2005;11:6012-6019.
• 18) Wang F, Reierstad S, Fishman DA. Matrilysin over-expression in MCF-7 cells enhances cellular invasiveness and pro-gelatinase activation. Cancer Lett 2006;236:292-301.
• 19) Nakopoulou L, Giannopoulou I, Lazaris A, et al. The favorable prognostic impact of tissue inhibitor of matrix metalloproteinases-1 protein overexpression in breast cancer cells. APMIS 2003;111(11):1027-1036.
• 20) Lam SW, Nota NM, Jager A, et al. Angiogenesis- and hypoxia-associated proteins as early indicators of the outcome in patients with metastatic breast cancer given first-line bevacizumab-based therapy. Clin Cancer Res 2016;22(7):1611-1620.
• 21) Degirmencioglu S, Ugurlu E, Yaren A. Clinical significance of serum vascular endothelial growth factor levels in patients with advanced non-small cell lung cancer. World Journal of Oncology Research 2017;4:7-11.