Presentation Authors: Kassem Faraj*, Kyle Rose, Melissa Stanton, Thai Ho, Alan Bryce, Douglas Lake, Phoenix, AZ, John Copland, Jacksonville, FL, Erik Castle, Phoenix, AZ
Introduction: Sarcomatoid features are present in about 5% of renal cell carcinoma (RCC) cases and have significant clinical implications, as patients are more likely to succumb to metastatic disease and experience dismal survival outcomes. The molecular behavior of sarcomatoid RCC (sRCC) is not fully understood, but previous reports have described a high prevalence of p53 mutations/overexpression, high proliferative capability, and expression of membrane receptors that influence cell growth. Patient-derived xenografts (PDX) are the most accurate models available to study tumor behavior. We describe our experience in using such a model to better characterize a case of chromophobe sRCC.
Methods: After IRB approval, a PDX was generated from a patient with metastatic chromophobe sRCC by implanting tumor tissue from two matched primary tumors and a metastatic retroperitoneal lymph node into the subcutaneous space of female nude mice. The cell lines developed were compared to the patient tumor, as well as to conventional cell line models (lung tissue induced to express PD-L1 and two separate cell lines of RCC). Comparisons were made histopathologically by a pathologist and molecularly using DNA sequencing and Western blot.
Results: When comparing the pathological characteristics between the specimens obtained from the patient (two primary tumor specimens, metastatic site) with the xenograft specimen, features were similar. Molecularly, DNA sequencing confirmed similar mutations and several DNA regions were compared between cell lines and matched, confirming that the mouse tumor accurately represented the original patient tumor. Western blot confirmed that sRCC cell lines all expressed greater PD-L1 compared to the conventional cell lines, confirming a prior series we reported.
Conclusions: SRCC is an aggressive variant with no established treatment approach once diagnosis is made. The presence of PD-L1 provides opportunities for potential targeted therapy, as a recent case study described efficacy of using PD-L1 inhibitors to the benefit of two patients with metastatic sRCC. PDX is valuable in generating tumor models that can be used for studying therapeutic options in rare, aggressive entities that are otherwise difficult to study in a randomized manner, such as sRCC.