Non-Clear Cell Renal Cell Carcinoma Strongly Associated With Proliferative Disease Subtypes

A notable association has been identified between non-clear cell renal cell carcinoma and proliferative disease.

Non-clear cell renal cell carcinoma (nccRCC) appears to have a strong association with proliferative disease subtypes and a weak association with angiogenic subtypes vs ccRCC, according to findings from an analysis of real-world RCC samples presented at the 2021 International Kidney Cancer Association North America meeting.

Findings from the research indicated that sarcomatoid/rhabdoid features had an association with T-effector/proliferative and stromal/proliferative disease subtypes. A microenvironment cell population counter analysis of the tumor microenvironment indicated that T-effector/proliferative samples tended to be associated with an increase in immune cell infiltration compared with other subgroups. Additionally, an increase in pro-immune cells coincided with a high expression of immune checkpoint genes in T-effector/proliferative subtypes. Immunosuppressive cells were most prevalent in stromal/proliferative subgroups, with endothelial cells most notable in angiogenic and angio/stromal subtypes.

Investigators assessed transcriptional profiles of real-world RCC patient samples utilizing DNA/RNA next-generation sequencing that were submitted to a commercial Caris Life Sciences–certified lab. Diagnoses were confirmed through central pathology review and subgroups were identified via weighted gene expression level averages.

Investigators collected and profiled a total of 657 samples. The median patient age was 62 years (range, 14-90) and most patients were men (70.6%). Disease subtypes included papillary (9.6%), chromophobe (4.6%), medullary (1.2%), collecting duct (0.9%), and mixed nccRCC subtypes (6.2%). Biopsies were done in the kidney (51.7%), lung (11.4%), bone (6.8%), lymph nodes (5.2%), liver (4.2%), and from other metastatic sites (20.7%).

Although the majority of provided samples were angiogenic or angio/stromal, the subtypes comprised less than 10% of nccRCC samples, the majority of which were proliferative. PD-L1 positivity rates were higher in nccRCC samples (range, 16.7%-37.5%) compared with ccRCC (12.0%), the highest rates of which were observed in medullary samples. Rates of mismatch repair deficiency/micro satellite instability–high and tumor mutational burden–higher rates were highest in collecting duct carcinoma (33.3%) and seldom occurred in all other histologic subgroups (3.5%).

Investigators believe that the findings from this trial have provided insights into creating personalized strategies for patients with nccRCC and further research in prospective clinical trials is needed. Notably, the trial was limited by small representation in certain disease subtypes.


Barata PC, Gulati S, Elliott A, et al. Gene expression profiling (GEP) of non-clear cell renal cell carcinoma (nccRCC) identifies a unique spectrum of transcriptional signatures with clinical potential. Presented at 2021 International Kidney Cancer Association North America; November 5-6, 2021; Austin, Texas. Abstract N26.