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

Gordana Đorđević orcid id orcid.org/0000-0002-2010-6203 ; Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia
Koviljka Matušan-Ilijaš ; Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia
Emina Sinožić ; Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia
Giuseppe Damante ; Dipartimento di Scienze e Tecnologie Biomediche, Universita degli Studi di Udine, Italy
Dora Fabbro ; Azienda Ospedaliero Universitaria S. Maria della Misericordia, Udine, Italy
Blaženka Grahovac ; Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia
Ksenija Lučin ; Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia
Nives Jonjić orcid id orcid.org/0000-0003-2995-0766 ; Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia


Puni tekst: engleski pdf 694 Kb

str. 608-617

preuzimanja: 473

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Sažetak

Aim To 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.
Methods We 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.
Results Cytoplasmic 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).
Conclusion Higher 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.

Ključne riječi

Carcinoma, Renal Cell, Nuclear Factor kappa B, Immunohistochemistry, Polymerase Chain Reaction, VEGF

Hrčak ID:

29274

URI

https://hrcak.srce.hr/29274

Posjeta: 845 *