Renal Medullary Carcinoma: A Recently Described Highly Aggressive Renal Tumor in Young Black Patients

e16096 Background: Renal medullary carcinoma (RMC) is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, primarily sickle cell trait. This is a rare and highly aggressive tumor that is shown to be most resistant to chemotherapy. In an effort to evaluate treatment outcomes, we retrospectively examined those patients diagnosed with RMC who were treated with and without bevacizumab based regimens. Methods: We reviewed the genitourinary medical oncology database at M. D. Anderson Cancer Center for patient diagnosed between 1999–2008 with histology proven RMC. Vital statistics of birth and death dates were noted. In addition, detailed chemotherapy regimen as well as medical and radiological data were also obtained. Results: All patients had metastatic disease (stage IV) to at least one distant site at presentation. Distant sites included bone, liver or lungs. A sample of five black males 5/9 (53%) were treated with therapy that included a 2 or 3 drug combinations of Adriamycin, Taxol, Gemzar, cisplatin, or Gleevac. Median survival was 12.7 months (3.2–22.2) while median age was 31 year (28–59). Only 4/9 (47%) patients received bevacizumab based therapy in a 2 or 3 drug combinations with Gemzar, Xeloda, cisplatin, or Taxol. In this group, 50% were females, median age of 36 years (33–39) and median survival of 18.5 months (15.5–22.8). Conclusions: Sickle cell trait was confirmed for all in this group diagnosed with RMC. 8/9 of these patients were black and 1/9 South-Asian. The group that received bevacizumab based therapy had a median survival of 5.8 months longer. Future studies, including genetic studies on the tumor types are essential to determining the SNP profiles of renal cell carcinoma in black patients. Furthermore, a prospective multicenter trial should be developed to evaluate the efficacy of bevacizumab based regimens in renal medullary carcinoma in this population. No significant financial relationships to disclose.

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Novel Patient Metastatic Pleural Effusion-Derived Xenograft Model of Renal Medullary Carcinoma Demonstrates Therapeutic Efficacy of Sunitinib

Frontiers in Oncology ◽

10.3389/fonc.2021.648097 ◽

2021 ◽

Vol 11 ◽

Author(s):

Alex Q. Lee ◽

Masami Ijiri ◽

Ryan Rodriguez ◽

Regina Gandour-Edwards ◽

Joyce Lee ◽

...

Keyword(s):

Pleural Effusion ◽

Therapeutic Efficacy ◽

First Generation ◽

Renal Tumor ◽

Treatment Options ◽

Xenograft Model ◽

Medullary Carcinoma ◽

Renal Medullary Carcinoma ◽

Pdx Model ◽

Two Generations

BackgroundRenal medullary carcinoma (RMC) is a rare but aggressive tumor often complicated by early lung metastasis with few treatment options and very poor outcomes. There are currently no verified RMC patient-derived xenograft (PDX) mouse models established from metastatic pleural effusion (PE) available to study RMC and evaluate new therapeutic options.MethodsRenal tumor tissue and malignant PE cells from an RMC patient were successfully engrafted into 20 NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. We evaluated the histopathological similarity of the renal tumor and PE PDXs with the original patient renal tumor and PE, respectively. We then evaluated the molecular integrity of the renal tumor PDXs between passages, as well as the PE PDX compared to two generations of renal tumor PDXs, by microarray analysis. The therapeutic efficacy of sunitinib and temsirolimus was tested in a serially-transplanted generation of 27 PE PDX mice.ResultsThe pathologic characteristics of the patient renal tumor and patient PE were retained in the PDXs. Gene expression profiling revealed high concordance between the two generations of renal tumor PDXs (RMC-P0 vs. RMC-P1, r=0.865), as well as between the first generation PE PDX and each generation of the renal tumor PDX (PE-P0 vs. RMC-P0, r=0.919 and PE-P0 vs. RMC-P1, r=0.843). A low number (626) of differentially-expressed genes (DEGs) was seen between the first generation PE PDX and the first generation renal tumor PDX. In the PE-P1 xenograft, sunitinib significantly reduced tumor growth (p<0.001) and prolonged survival (p=0.004) compared to the vehicle control.ConclusionsA metastatic PE-derived RMC PDX model was established and shown to maintain histologic features of the patient cancer. Molecular integrity of the PDX models was well maintained between renal tumor and PE PDX as well as between two successive renal tumor PDX generations. Using the PE PDX model, sunitinib demonstrated therapeutic efficacy for RMC. This model can serve as a foundation for future mechanistic and therapeutic studies for primary and metastatic RMC.

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