Adela Maria Ferician1, Ovidiu Catalin Ferician2, Andrei Dragos Cumpanas3,4, Patricia Lorena Berzava3,4, Alexandru Nesiu5, Ariana Barmayoun6, Anca Maria Cimpean3,4,7. 1. Department of Orthopedy and Traumatology/Urology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. 2. Department of Orthopedy and Traumatology/Urology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania; ovidiu.ferician@yahoo.com ancacimpean1972@yahoo.com acimpeanu@umft.ro. 3. Department of Microscopic Morphology/Histology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. 4. Angiogenesis Research Center, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania. 5. Department of Urology, Faculty of Medicine "Vasile Goldiş" Western University, Arad, Romania. 6. Klinik fur Psychiatrie, Psychosomatik und Psychotherapie, Uniklinikum Frankfurt, Frankfurt, Germany. 7. Center of Expertise for Rare Vascular Disease in Children, Emergency Hospital for Children Louis Turcanu, Timisoara, Romania.
Abstract
BACKGROUND/AIM: We previously described four different vascular patterns (reticular, diffuse, fasciculate, and trabecular) in renal cell carcinoma (RCC) suggesting an early and heterogeneous acquisition of perivascular cells most probably due to a particular PDGF pathway gene expression profile. The aim of the study was to study PDGF pathway gene expression profiles, separately for each vascular pattern. MATERIALS AND METHODS: TaqMan assay for the PDGF pathway was performed on twelve cases of ccRCC previously evaluated by histopathology, immunohistochemistry, and RNAscope. Gene expression profile was correlated with grade, invasion, vascular patterns, and VEGF. RESULTS: PIK3C3 and SLC9A3 genes were overexpressed in all vascular patterns, but they were significantly correlated with high VEGF mRNA in the reticular and diffuse pattern. STAT1, JAK2, SHC2, SRF and CHUK (IKK) were exclusively overexpressed in cases with diffuse vascular pattern. SLC9A3, CHUK and STAT3 were overexpressed in G2 tumors. CONCLUSION: Three ccRCC subgroups were defined: 1) PIK3C3 (VSP34)/SLC9A3 which may be proper for anti PIK3C3 inhibitors; 2) VEGFhigh subgroup where association of anti VEGF may be a benefit and 3) JAK2/STAT1 subgroup, potentially being eligible for anti JAK/STAT therapy associated with IKK inhibitors.
BACKGROUND/AIM: We previously described four different vascular patterns (reticular, diffuse, fasciculate, and trabecular) in renal cell carcinoma (RCC) suggesting an early and heterogeneous acquisition of perivascular cells most probably due to a particular PDGF pathway gene expression profile. The aim of the study was to study PDGF pathway gene expression profiles, separately for each vascular pattern. MATERIALS AND METHODS: TaqMan assay for the PDGF pathway was performed on twelve cases of ccRCC previously evaluated by histopathology, immunohistochemistry, and RNAscope. Gene expression profile was correlated with grade, invasion, vascular patterns, and VEGF. RESULTS: PIK3C3 and SLC9A3 genes were overexpressed in all vascular patterns, but they were significantly correlated with high VEGF mRNA in the reticular and diffuse pattern. STAT1, JAK2, SHC2, SRF and CHUK (IKK) were exclusively overexpressed in cases with diffuse vascular pattern. SLC9A3, CHUK and STAT3 were overexpressed in G2 tumors. CONCLUSION: Three ccRCC subgroups were defined: 1) PIK3C3 (VSP34)/SLC9A3 which may be proper for anti PIK3C3 inhibitors; 2) VEGFhigh subgroup where association of anti VEGF may be a benefit and 3) JAK2/STAT1 subgroup, potentially being eligible for anti JAK/STAT therapy associated with IKK inhibitors.