Uterin leyomiyomlarda vasküler endotelyal büyüme faktörü ve matriks metalloproteinaz-2 ekspresyonu ve anjiyogenezle ilişkisi

Year 2011, Volume: 18 Issue: 3, 86 - 91, 30.09.2011

Çiğdem Tokyol , Fatma Aktepe , Fatma Dilek , Mehmet Yılmazer

Abstract

Amaç: Leyomiyom uterusun en sýk görülen tümörüdür. Uterin leyomiyomun büyümesinde anjiyogenik faktörler ve proteazlar rol oynayabilir. Çalýþmamýzýn amacý uterin leyomiyomlarda vasküler endotelyal büyüme faktörü (VEGF) ve matriks metalloproteinaz-2 (MMP-2) ekspresyonunu araþtýrmak ve mikrodamar yoðunluðu (MVD) ile olasý iliþkilerini belirlemekti. Gereç ve yöntemler: Çalýþma materyali leyomiyom nedeni ile opere edilmiþ 50 hastanýn leyomiyom ve normal miyometriyumunu içeren parafin bloklardan oluþuyordu. VEGF, MMP-2 ve CD34 ekspresyonu immünohistokimyasal olarak çalýþýldý. VEGF ve MMP-2 ye ait immünohistokimyasal yöntemle elde edilen bulgular semikantitatif analiz ile deðerlendirildi. MVD ise, CD34 pozitif vasküler endotelyal hücreleri sayarak hesaplandý. Bulgular: Leyomiyomlardaki VEGF ve MMP-2 ekspresyonu normal miyometriyuma göre anlamlý olarak daha yüksek bulundu (p=0.001). CD34 boyamasý MVD nun leyomiyomlarda miyometriyuma göre daha az olduðunu gösterdi (p<0.05). VEGF ve MMP-2 boyanmasý ile MVD arasýnda korelasyon saptanmadý. Sonuç: Bu bulgular uterin leyomiyomlarýn patogenezinde VEGF ve MMP-2 nin rol oynayabileceðini düþündürmüþtür. Bu hastalýðýn geliþim sürecine anjiyogenez dýþýndaki bazý faktörler de katkýda bulunabilir.

Keywords

Uterus, leyomiyom, VEGF, MMP-2, mikrodamar yoðunluðu

Expression of vascular endothelial growth factor and matrix metalloproteinase-2 in uterine leiomyoma and correlation with angiogenesis

Abstract

Objective: Leiomyoma is the most common tumor of the uterus. Angiogenic factors and proteases may play role in the growth of uterine leiomyoma.The aim of our study was to investigate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in uterine leiomyoma and their possible relation to microvessel density (MVD). Material and methods: Material for the study comprised parafin-embedded tissue sections of uterine leiomyomas and corresponding myometrium derived from 50 hysterectomized women. VEGF, MMP-2 and CD34 expression was investigated immunohistochemically. Semiquantitative analysis of the immunostainings for VEGF and MMP-2 was performed. MVD was calculated by counting of CD34 positive vascular endothelial cells. Results: Expression of VEGF and MMP-2 was significantly higher in leiomyomas than corresponding myometrium (p=0.001). The CD34 labeling showed decreased MVD in leiomyomas compared with myometrium (p<0.05). There was no correlation between VEGF and MMP-2 staining and MVD. Conclusion: These data suggested that VEGF and MMP-2 may play role in the development of uterine leiomyomas. Mechanisms other than promotion of angiogenesis may contribute to this disease process.

Keywords

Uterus, leiomyoma, VEGF, MMP-2, microvessel density

References

• Zaloudek C, Hendrickson MR. Mesenchymal tumors of the uterus. In: Kurman RJ, ed. Blaustein’ s Pathology of the Female Genital Tract (5th Ed) New York, Springer-Verlag, 2002; 561-615.
• Okolo S. Incidence, aetiology and epidemiology of uterine fibroids. Best Pract Res Clin Obstet Gynaecol 2008; 22(4): 571-88.
• Balcý O, Çolakoðlu MC, Özdemir S. Benign diseases of the uterine corpus. Türkiye Klinikleri J Surg Med Sci 2007; 3(40): 27-35.
• Stewart EA, Nowak RA. Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era. Hum Reprod Update 1996; 2(4): 295-306.
• Kumar V, Abbas AK, Fausto N. Tissue Renewal and
• Repair: Regeneration, Healing, and Fibrosis. In: Kumar V, Abbas AK, Fausto N, eds. Robbins Pathologic Basis of Disease (7th Ed) China, Elsevier Saunders, 2005; 87-118.
• Hulboy DL, Rudolf LA, Matrisian LM. Matrix metalloproteinases as mediators of reproductive function. Mol Hum Reprod 1997; 3(1): 27-45.
• Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem 1999; 274(31): 21491-4.
• Coussens LM, Werb Z. Matrix metalloproteinases and the development of cancer. Chem Biol 1996; 3(11): 895-904.
• Rundhaug JE. Matrix metalloproteinases and angiogenesis. J Cell Mol Med 2005; 9(2): 267-85.
• Noyes RW, Hertig AT, Rock JR. Dating the endometrial biopsy. Am J Obstet Gynecol 1975; 122(2): 262-3.
• Sun WH, Sun YL, Fang RN, Shao Y, Xu HC, Xue QP, et al. Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis. Jpn J Clin Oncol 2005; 35(12): 707-13.
• Weidner N, Semple JP, Welch WR, Folkman J. Tumour angiogenesis and metastases- correlation in invasive breast carcinoma. N Engl J Med 1991; 324(1): 1-8.
• Bosari S, Lee AK, DeLellis RA, Wiley BD, Heatley GJ, Silverman ML. Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol 1992; 23(7): 755-61.
• Torry RJ, Rongish BJ. Angiogenesis in the uterus: potential regulation and relation to tumor angiogenesis. Am J Reprod Immunol 1992; 27(3-4): 171-9.
• Zhang L, Rees MCP, Bicknell R. The isolation and long term culture of normal human endometrial epithelium and stroma: expression of mRNAs for angiogenic polypeptides basally and on oestrogen challenge. J Cell Sci 1995; 108(Pt 1): 323-31.
• Harrison-Woolrych ML, Sharkey AM, Charnock-Jones DS, Smith SK. Localization and quantification of vascular endothelial growth factor messenger ribonucleic acid in human myometrium and leiomyomata. J Clin Endocrinol Metab 1995; 80(6): 1853-8.
• Dixon D, He H, Haseman JK. Immunohistochemical localization of growth factors and their receptors in uterine leiomyomas and matched myometrium. Environ Health Perspect 2000; 108(suppl 5): 795-802.
• Poncelet C, Madelenat P, Feldmann G, Walker F, Darai
• E. Expression of von Willebrand’ s factor, CD34, CD31, and vascular endothelial growth factor in uterine leiomyomas. Fertil Steril 2002; 78(3): 581-6.
• Özçakýr HT, Baytur Y, Giray G, Uyar Y, Özbilgin K,
• Çaðlar H. Leiomyom ve normal myometriumda immunohistokimyasal vasküler endotelyal growth factor (VEGF) ekspresyonu. Türk Fertilite Dergisi 2003; 11(4): 299-304.
• Gentry CC, Okolo SO, Fong LF, Crow JC, Maclean AB, Perrett CW. Quantification of vascular endothelial growth factor-A in leiomyomas and adjacent myometrium. Clin Sci 2001; 101(6): 691-5.
• Fujita M. Histological and biochemical studies of collagen in human uterine leiomyomas. Hokkaido Igaku Zasshi 1985; 60(4): 602-15.
• Wegrowski Y, Bellon G, Quereux C, Maquart F-X. Biochemical alterations of uterine leiomyoma extracellular matrix in type IV Ehlers-Danlos syndrome. Am J Obstet Gynecol 1999; 180(4): 1032-4.
• Bogusiewicz M, Stryjecka-Zimmer M, Postawski K, Jakimiuk AJ, Rechberger T. Activity of matrix metalloproteinase-2 and -9 and contents of their tissue inhibitors in uterine leiomyoma and corresponding myometrium. Gynecol Endocrinol 2007; 23(9): 541- 6.
• Wolañska M, Sobolewski K, Bañkowski E, Jaworski S. Matrix metalloproteinases of human leiomyoma in various stages of tumor growth. Gynecol Obstet Invest 2004; 58(1): 14-8.
• Casey R, Rogers PA, Vollenhoven BJ. An immunohistochemical analysis of fibroid vasculature. Hum Reprod 2000; 15(7): 1469-75.
• Walocha JA, Litwin JA, Miodoñski AJ. Vascular system of intramural leiomyomata revealed by corrosion casting and scanning electron microscopy. Hum Reprod 2003; 18(5): 1088-93.