![]() ![]() We evaluated the genome of the angiogenic and immunoexpression patterns in 512 clearRCC cases included in the Kidney Renal Clear Cell Carcinoma study (PanCancer Atlas, TCGA) and additionally focused on CD31 ( PECAM1), CD274 and CD8A expression. Moreover, recent adjuvant therapies have been proposed and approved in locally advanced renal cancer, as pembrolizumab treatment has led to a significant improvement in disease-free survival compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. In view of this, it is imperative that there is some certainty that sections taken from cases of clearRCC are representative of the tumor with prognostic parameters that will reflect outcome. The advent of immunotherapy based upon immune checkpoint blockade, in addition to the development of drugs that target angiogenesis, has meant that it has become increasingly important to determine which patients with advanced disease are best treated by these adjuvant therapies. Several studies have investigated the vascularity of clearRCC with varying results, and as a consequence, our understanding of the assessment of genetic signatures and patterns of angiogenesis for clearRCC is in evolution. In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity. Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods ( p = 0.04). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes ( p = 0.03). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion ( p = 0.03). ![]() Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). Routine 5231 tissue blocks were obtained. Angiogenic and immune markers were tested. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). ![]() First, usual standard sampling was applied (1 block/cm of tumor) second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. One hundred cases of clearRCC were sampled. We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). ![]()
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