Naslov (srp)

Ekspresija hemokinske osovine CXCL12/CXCR4/CXCR7, markera hipoksije i angiogeneze u karcinomima bubrežnog parenhima

Autor

Floranović, Milena Potić-,

Doprinosi

Janković-Veličković, Ljubinka, 1960-
Jovičić Milentijević, Maja
Radojević Škodrić, Sanja

Opis (srp)

Renal cell carcinoma (RCC) is the most common kidney cancer.Even though it represents 5% of all cancer diagnosis, it is consideredone of the most lethal urologic malignancies. The most commonsubtype is clear cell RCC and the second in frequency is papillary RCC.At diagnosis 23% of patients already have metastatic disease and 25%will develop metastases within five years from nephrectomy. Up to date,all the factors that affect the development and prognosis of these tumorsare still not fully clarified. Over the last decade, various biomarkershave been studied in order to elucidate the behavior of RCC but noconsensus has been achieved.In this study we immunohistochemically examined theexpression of chemokine CXCL12 and its receptors CXCR4 andCXCR7 on 98 paraffin embedded RCC samples obtained after radicalnephrectomy. We have also studied the expression of Hypoxia induciblefactor 1α, which regulates cell survival in hypoxic conditions, andNotch1 receptor, which is the component of the conservative Notchsignaling pathway. The localization, percentage and the intensity of theexpression of these biomarkers were studied with the application ofhistoscore. We analyzed their co-expression and their association withclinical and pathological parameters and survival of the patients.Positive membranous and cytoplasmatic CXCL12 and CXCR7expression was present in over 90% of the samples, while about 60%expressed positive CXCR4 staining.We found association betweentumor size and higher cytoplasmatic CXCL12 and CXCR7 expression.Over 70% of the samples were HIF1α positive, and higher values ofcytoplasmatic HIF1α histoscore were associated with higher tumorgrade. We also found the association between necrosis andcytoplasmatic CXCR7, HIF1α and Notch1 histoscore.Compared to ccRCC in pRCC significantly higher values ofmembranous CXCL12 as well as cytoplasmatic CXCL12, CXCR4,CXCR7 and HIF1α histoscore can be expected. CCRCC has 4 timeshigher probability of positive membranous CXCR4 expression and 20 times higher probability of positive membranous Notch1 eexpression.H higher membranous Notch1 histoscore is expected in cccRCC as well.Strong positive correlation was found between cyoplasmaticHIF1α histoscore and cytoplasmatic CXCL12 and CXCR7 histoscores,suggesting their co expression and potential interaction.Shorter survival can be predicted by higher clinical stage, thevalue of CXCL12 cytoplasmatic histoscore above 73 and by highervalues of membranous CXCR7 histoscore.Examining the roles of these biomarkers in RCC could in thefuture bring useful implications in diagnosis, prognosis, prevention ofthe recidives and the development of target therapy in the most lethalurologic malignancy.

Opis (srp)

Biografija autora: list 113,Bibliografija: listovi 96-112. Datum odbrane: Pathology

Jezik

srpski

Datum

2021

Licenca

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Creative Commons CC BY-NC-ND 3.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 3.0 Austria License.

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