IMUNOHISTOHEMIJSKA EKSPRESIJA VASKULARNOG ENDOTELNOG FAKTORA RASTA U ADENOKARCINOMU PROSTATE
Abstract
Uvod: Adenokarcinom je najčešći tumor prostate. Kliničko-morfološki prognostički faktori su Glisonov (Gleason) skor, TNM klasifikacija i invazija limfnih čvorova. Vaskularni endotelni faktor rasta (VEGF) je induktor angiogeneze, koja ima značajnu ulogu u rastu i metastaziranju tumora. Pokazano je da u ćelijama adenokarcinoma postoji ekspresija VEGF.
Cilj rada: Cilj rada je da se analizira obim imunohistohemijske ekspresije VEGF u adenokarcinomu prostate i povezanost između ekspresije VEGF i kliničko-morfoloških prognostičkih faktora na uzorku pacijenata lečenih u Kliničko-bolničkom centru „Dr Dragiša Mišović“ u Beogradu.
Materijal i metode: U ovom radu korišćen je operativni materijal 20 slučajeva adenokarcinoma prostate, dobijenih radikalnom prostatektomijom. Za određivanje stadijuma tumora korišćena je TNM klasifikacija iz 2002. godine, a za određivanje gradusa korišćen je Glisonov skor iz 2009. Imunohistohemijsko bojenje adenokarcinoma prostate ocenjivano je semikvantitativno.
Rezultati: Ekspresija VEGF je bila prisutna kod svih analiziranih adenokarcinoma prostate. Kod petnaest od analiziranih dvadeset (75%) bila je difuzna, a kod pet je bila umerena (25%). Učestalost difuzne eskpresije VEGF je bila statistički značajno veća kod Glisonovog skora od 8 do 10, u odnosu na Glisonov skor 7 (p < 0,01). Kod postojanja limfnih metastaza i TNM stadijuma III i IV učestalost difuzne ekspresije VEGF je veća, ali ne i statistički značajna.
Zaključak: Difuzna ekspresija VEGF, na uzorku pacijenata lečenih u KBC „Dr Dragiša Mišović“ u Beogradu, češće je uočena kod adenokarcinoma prostate sa višim Glisonovim skorom i višim stadijumom, kao i kod postojanja tumorske invazije limfnih čvorova, što je u skladu sa ranijim istraživanjima.
Ključne reči: Adenokarcinom prostate, VEGF, Glisonov skor, TNM klasifikacija
References
Fletcher CD. Diagnostic Histopathology of Tumors: 2-Volume Set with CD-ROMs: Elsevier Health Sciences; 2007. p. 733-81.
Mihajlović J, Pechlivanoglou P, Miladinov-Mikov M, Živković S, Postma MJ. Cancer incidence and mortality in Serbia 1999–2009. BMC Cancer. 132013. p. 18.
Eble JN. Pathology and genetics of tumours of the urinary system and male genital organs: Iarc; 2004. p. 159-214.
Freedland SJ, Amling CL, Terris MK, Presti JC, Jr., Aronson WJ, Elashoff D, et al. Is there a difference in outcome after radical prostatectomy between patients with biopsy Gleason sums 4, 5, and 6? Results from the SEARCH database. Prostate Cancer Prostatic Dis. 2003;6(3):261-5.
Tsao CK, Gray KP, Nakabayashi M, Evan C, Kantoff PW, Huang J, et al. Patients with Biopsy Gleason 9 and 10 Prostate Cancer Have Significantly Worse Outcomes Compared with Gleason 8 Disease. J Urol. 2015;134(4):439-50.
Albertsen PC, Fryback DG, Storer BE, Kolon TF, Fine J. Long-term survival among men with conservatively treated localized prostate cancer. Jama. 1995;274(8):626-31.
Egevad L, Granfors T, Karlberg L, Bergh A, Stattin P. Prognostic value of the Gleason score in prostate cancer. BJU Int. 2002;89(6):538-42.
Atanackovic M, Bacetic D, Basta-Jovanivic G, Boricic I, Brasanac D, Laban A, et al. Patologija. Beograd: Medicinski fakultet Univerziteta u Beogradu Katedra za Patologiju; 2006. p. 644-6.
Cheng L, Jones TD, Lin H, Eble JN, Zeng G, Carr MD, et al. Lymphovascular invasion is an independent prognostic factor in prostatic adenocarcinoma. J Urol. 2005;174(6):2181-5.
Erkal EY, Bora H, Tepeoglu M, Akmansu M. Role of vascular endothelial growth factor in clinically localized prostate cancer treated with radiation therapy. Balkan Med J. 2014;31(1):43-9.
Luczynska E, Gasinska A, Wilk W. Microvessel density and expression of vascular endothelial growth factor in clinically localized prostate cancer. Pol J Pathol. 2013;64(1):33-8.
Wong SY, Haack H, Crowley D, Barry M, Bronson RT, Hynes RO. Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis. Cancer Res. 2005;65(21):9789-98.
Eichelberger LE, Cheng L. Does pT2b prostate carcinoma exist? Critical appraisal of the 2002 TNM classification of prostate carcinoma. Cancer. 2004;100(12):2573-6.
Helpap B, Egevad L. Modified Gleason grading. An updated review. Histol Histopathol. 2009;24(5):661-6.
Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82(1):4-6.
Nordby Y, Andersen S, Richardsen E, Ness N, Al-Saad S, Melbo-Jorgensen C, et al. Stromal expression of VEGF-A and VEGFR-2 in prostate tissue is associated with biochemical and clinical recurrence after radical prostatectomy. Prostate. 2015;75(15):1682-93.
Boddy JL, Fox SB, Han C, Campo L, Turley H, Kanga S, et al. The androgen receptor is significantly associated with vascular endothelial growth factor and hypoxia sensing via hypoxia-inducible factors HIF-1a, HIF-2a, and the prolyl hydroxylases in human prostate cancer. Clin Cancer Res. 2005;11(21):7658-63.
Pallares J, Rojo F, Iriarte J, Morote J, Armadans LI, de Torres I. Study of microvessel density and the expression of the angiogenic factors VEGF, bFGF and the receptors Flt-1 and FLK-1 in benign, premalignant and malignant prostate tissues. Histol Histopathol. 2006;21(8):857-65.
Ferrer FA, Miller LJ, Andrawis RI, Kurtzman SH, Albertsen PC, Laudone VP, et al. Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vitro expression of VEGF by human prostate cancer cells. J Urol. 1997;157(6):2329-33.
El-Gohary YM, Silverman JF, Olson PR, Liu YL, Cohen JK, Miller R, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in prostatic adenocarcinoma. Am J Clin Pathol. 2007;127(4):572-9.
Kollermann J, Helpap B. Expression of vascular endothelial growth factor (VEGF) and VEGF receptor Flk-1 in benign, premalignant, and malignant prostate tissue. Am J Clin Pathol. 2001;116(1):115-21.
Mak P, Leav I, Pursell B, Bae D, Yang X, Taglienti CA, et al. ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading. Cancer Cell. 2010;17(4):319-32.
Strohmeyer D, Strauss F, Rossing C, Roberts C, Kaufmann O, Bartsch G, et al. Expression of bFGF, VEGF and c-met and their correlation with microvessel density and progression in prostate carcinoma. Anticancer Res. 2004;24(3a):1797-804.
Ismail AH, Altaweel W, Chevalier S, Kassouf W, Aprikian AG. Expression of vascular endothelial growth factor-A in human lymph node metastases of prostate cancer. Can J Urol. 2004;11(1):2146-50.