title: Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior.
abstract: Renal medullary carcinoma is a rare, well-recognized highly aggressive tumor of varied histopathology, which occurs in young patients with sickle cell trait or disease. Rhabdoid elements, occasionally seen in high-grade renal tumors including renal medullary carcinoma, possibly represent a pathologic marker of aggressive behavior. INI1 (hSNF5/SMARCB1/BAF47) is a highly conserved factor in the ATP-dependent chromatin-modifying complex. Loss of this factor in mice results in aggressive rhabdoid tumors or lymphomas. In humans, the loss of INI1 expression has been reported in pediatric renal rhabdoid tumors, central nervous system atypical teratoid/rhabdoid tumors and epithelioid sarcomas, a possible primary soft tissue rhabdoid tumor. This study compares five renal medullary carcinomas with 10 high-grade renal cell carcinomas (five with rhabdoid features), two urothelial carcinomas and two pediatric renal rhabdoid tumors. All five renal medullary carcinomas, irrespective of histopathology, showed complete loss of INI1 expression similar to that seen in pediatric renal rhabdoid tumors. In contrast, all renal cell carcinomas or urothelial carcinomas, including those with histological rhabdoid features, expressed INI1. Clinically, all five of the patients with renal medullary carcinoma and the two patients with rhabdoid tumors presented with extra-renal metastases at the time of diagnosis. This study demonstrates that renal medullary carcinoma and renal rhabdoid tumor share a common molecular/genetic alteration, which is closely linked to their aggressive biological behavior. However, the absence of INI1 expression is not necessarily predictive of rhabdoid histopathology but remains associated with aggressive behavior in renal medullary carcinoma.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jason X
authors.initials: JX
authors.lastname: Cheng
authors.forename: Maria
authors.initials: M
authors.lastname: Tretiakova
authors.forename: Can
authors.initials: C
authors.lastname: Gong
authors.forename: Saptarshi
authors.initials: S
authors.lastname: Mandal
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Taxy
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018335:Rhabdoid Tumor / Q000378:metabolism / Q000473:pathology*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors