Emina Sinožić

University of Rijeka

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GĐ

Gordana Đorđević

University of Kragujevac

Koviljka Matušan‐Ilijaš

University of Rijeka

Nives Jonjić

University of Rijeka

Blaženka Grahovac

University of Rijeka

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Željko Fučkar

Klinički Bolnički Centar Rijeka

Kristian Krpina

University Hospital Centre Zagreb

Dora Fabbro

Ospedale Santa Maria della Misericordia di Udine

Ksenija Lučin

University of Rijeka

Vjekoslav Peitl

Catholic University of Croatia

Gordana Djordjević

University of Kragujevac

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University of Rijeka

Klinički Bolnički Centar Rijeka

University Hospital Centre Zagreb

Ministry of Health

University of Kragujevac

University of Nis

Klinički centar Niš

Ospedale Santa Maria della Misericordia di Udine

University of Udine

University of Trieste

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C124 NK cell immunohistochemistry – a new prognostic marker of bladder cancer recurrence?

European Urology Supplements (2009)

Kristian Krpina Emina Sinožić Gordana Djordjević Nives Jonjić Željko Fučkar

10.1016/s1569-9056(09)75149-8

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Relationship Between Vascular Endothelial Growth Factor and Nuclear Factor-κB in Renal Cell Tumors

Croatian Medical Journal (2008)

Gordana Đorđević Koviljka Matušan‐Ilijaš Emina Sinožić Giuseppe Damante Dora Fabbro

AimTo assess the relationship between protein and messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and subcellular localization of nuclear factor-kappa B (NF-κB), proliferation rate of tumor cells, and clinicopathological characteristics of renal cell tumors.MethodsWe analyzed 31 one renal cell tumors – 22 clear cell renal cell carcinomas (CCRCC) and 9 other histologic types (non-CCRCC). VEGF expression and subcellular localization of p65 member of NF-κB and Ki67 were immunohistochemically evaluated for the proliferation rate of tumor cells. Expression of VEGF mRNA was assessed using quantitative real-time polymerase chain reaction after total RNA extraction from snap-frozen tumor tissue samples.ResultsCytoplasmic localization of VEGF protein in renal cell tumors showed a perimembranous and diffuse pattern, the former being more evident in CCRCC (27.1 ± 18.9 vs 3.3 ± 10 % tumors, P = 0.001) and the latter in non-CCRCC type (71.7 ± 23.2 vs 31.1 ± 22.1 % tumors, P < 0.001). Heterogeneity in VEGF gene expression was more pronounced in CCRCC type than in non-CCRCC type (P = 0.004). In addition, perimembranous VEGF pattern was associated with higher VEGF mRNA levels (P = 0.006) and diffuse VEGF pattern with lower VEGF mRNA levels (P < 0.001). Nuclear and cytoplasmic staining of NF-κB/p65 was observed in the majority of tumor cells. A significant association was recorded between cytoplasmic NK-κB/65 staining and VEGF staining of diffuse pattern (P = 0.026). Association between NF-κB/65 and proliferation rate of tumor cells was significant for cytoplasmic staining (P = 0.039) but not for nuclear NFkB/p65 staining (P = 0.099).ConclusionHigher but inhomogeneous expression of VEGF in tumor cells, especially in CCRCCs, is associated with NF-κB/65 activity. This indicates that both VEGF and NF-κB/65 may be important in renal carcinogenesis, representing a possible molecular target in the treatment of renal cell carcinoma.

10.3325/cmj.2008.5.608

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Expression of VEGF-A, VEGF-C and HIF-α in renal cell carcinoma

Gordana Đorđević Emina Sinožić Koviljka Matušan‐Ilijaš

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Vascular endothelial growth factor in relation to nuclear factor – kappa B in renal cell carcinoma

Gordana Đorđević Koviljka Matušan‐Ilijaš Emina Sinožić Vanja Licul Blaženka Grahovac

Renal cell carcinoma (RCC) is a malignancy with variable clinical course, partly attributable to specific genetic alterations of the different RCC types. Angiogenesis is important for tumor progression and metastatic spread. VEGF is a major factor which regulates angiogenesis while the nuclear factorkappaB(NF-kB), a family of transcription factors ; regulate a wide variety of cellular processes including cell growth, differentiation and apoptosis. The aim of this study was to evaluate the expression level of VEGF and to compare their values with the subcellular localization of NF-kB, proliferative rate of tumor cells and clinicopathological characteristics of RCC. Immunohistochemical evaluation included VEGF expression, the subcellular localization of p65 member of NF-kB and Ki67 for proliferative rate of tumor cells in series of 16 RCC. Total RNA was extracted from the same tumor tissue samples, previously snap-frozen. Expression of VEGF was analyzed using quantitative Real-time PCR. The difference in VEGF mRNA levels between conventional (11 clear cell RCC) and other histological types of RCC was not significant. Preliminary results indicate a more pronounce heterogeneity in VEGF expression within the group of clear cell RCC. VEGF mRNA levels show some positive association with VEGF protein expression evaluated as the percentage of positive cells and intensity of staining within the cells, while there was no association with NF-kB and Ki67. Larger tumors were characterized with higher value of VEGF expression, NF-kB and Ki67 and, moreover, the proliferation rate of tumor cells was higher in tumors with higher VEGF expression. Preliminary results indicate the heterogeneity in VEGF expression in conventional type of RCC. The association with tumor progression (tumor size and proliferation rate) indicates that VEGF is an important angiogenic factor in RCC. Although no association between NF-kB activity, VEGF expression and Ki67 was found on a small number of analyzed samples, our preliminary data suggest that the NF-kB may be important factor in renal carcinogensis by controlling cells proliferation. These findings need further validation of usefulness of NF-kB as a prognostic factor in RCC.

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PATOLOGIJA U UROLOGIJI

Medicina-buenos Aires (2004)

Gordana Đorđević Vjekoslav Peitl Emina Sinožić Elvira Mustać

The finality of all the pathological studies is not restricted to a diagnosis but a prognosis and a biological evaluation is demanded. For this reason the information transfer from the pathological report to the urologist can improve the communication among doctors and institutions. The aim of the paper was to describe the role of pathology in urology. In this part we consider protocols for handling and reporting renal cell carcinoma, bladder carcinoma and prostatic carcinoma. We also give the prevalence of these tumors in our region

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