SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma

Am J Surg Pathol. 2008 Aug;32(8):1168-74. doi: 10.1097/PAS.0b013e318161781a.

Abstract

Several previous studies have demonstrated the lack of SMARCB1/INI1 protein expression in only the malignant rhabdoid tumor (MRT). Several sarcoma groups are associated with a tumor-specific translocation involving EWS. Moreover, the EWS and SMARCB1/INI1 genes are located on the same 22q chromosome. We analyzed the status of SMARCB1/INI1 protein expression in 93 cases of sarcomas associated with chromosomal translocation involving EWS, comprising 52 Ewing's sarcoma/primitive neuroectodermal tumors, 24 extraskeletal myxoid chondrosarcomas (EMCS), 14 clear cell sarcomas of soft tissue, 2 desmoplastic small round cell tumors, and 1 myxoid/round cell liposarcoma. In addition, we analyzed the detailed SMARCB1/INI1 gene alteration in cases, which lacked its protein expression. Consequently, 4 EMCS showed no SMARCB1/INI1 expression, and 2 of these 4 cases revealed homozygous deletion and frameshift mutation of the SMARCB1/INI1 gene, respectively. These cases showed histologic findings compatible with EMCS, according to the most recent WHO classification, but no major fusion gene transcripts were detected. Moreover, 3 out of 4 SMARCB1/INI1 negative variant EMCS disclosed rhabdoid features. Therefore, the lack of SMARCB1/INI1 protein expression may be associated with rhabdoid features. The immunohistochemical result of the SMARCB1/INI expression is not an absolute diagnostic criteria for MRT and careful histologic evaluation is required to make a precise diagnosis of MRT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chondrosarcoma / chemistry*
  • Chondrosarcoma / genetics
  • Chondrosarcoma / mortality
  • Chondrosarcoma / pathology
  • Chromosomal Proteins, Non-Histone / analysis*
  • Chromosomal Proteins, Non-Histone / genetics
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Liposarcoma, Myxoid / chemistry
  • Liposarcoma, Myxoid / genetics
  • Neuroectodermal Tumors, Primitive / chemistry
  • Neuroectodermal Tumors, Primitive / genetics
  • Oncogene Proteins, Fusion / genetics*
  • Prognosis
  • RNA-Binding Protein EWS / genetics*
  • Reproducibility of Results
  • Rhabdoid Tumor / chemistry*
  • Rhabdoid Tumor / genetics
  • Rhabdoid Tumor / mortality
  • Rhabdoid Tumor / pathology
  • SMARCB1 Protein
  • Sarcoma / chemistry*
  • Sarcoma / genetics
  • Sarcoma / mortality
  • Sarcoma / pathology
  • Sarcoma, Clear Cell / chemistry
  • Sarcoma, Clear Cell / genetics
  • Sarcoma, Ewing / chemistry
  • Sarcoma, Ewing / genetics
  • Transcription Factors / analysis*
  • Transcription Factors / genetics
  • Translocation, Genetic*

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Oncogene Proteins, Fusion
  • RNA-Binding Protein EWS
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors