Loss of BRM expression is a frequently observed event in poorly differentiated clear cell renal cell carcinoma

Qiu-Yuan Xia1, Qiu Rao, Liang Cheng

  • 1Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Histopathology
|January 30, 2014
PubMed
Abstract

Insights

Loss of Brahma (BRM) expression is common in poorly differentiated clear cell renal cell carcinomas (RCCs). This finding suggests BRM loss may drive tumor de-differentiation and progression in clear cell RCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The SWI/SNF chromatin remodeling complex plays a crucial role in gene regulation.
  • Brahma (BRM) is a key catalytic subunit of the SWI/SNF complex.
  • Alterations in SWI/SNF subunits are implicated in various cancers.

Purpose of the Study:

  • To investigate the expression status of Brahma (BRM) in clear cell renal cell carcinomas (RCCs).
  • To analyze the histopathology, immunophenotype, molecular characteristics, and prognosis of BRM-negative clear cell RCC cases.
  • To understand the potential role of BRM loss in tumor de-differentiation and progression.

Main Methods:

  • Retrospective analysis of 625 clear cell RCC cases.
  • Identification of tumors lacking BRM expression.
  • Histopathological and immunophenotypic assessment.
  • Analysis of VHL gene mutations and chromosome 3p deletions.
  • Detection of chromosome polysomy.

Main Results:

  • 19 cases (3%) of grade 4 clear cell RCCs lacked BRM expression.
  • These BRM-negative tumors exhibited poor differentiation, with 13 showing pure poorly differentiated morphology and six being composite tumors.
  • VHL mutations (47%) and chromosome 3p deletions (in 11/13 poorly differentiated and all composite tumors) were observed.
  • Poorly differentiated areas showed chromosome 3 polysomy, while low-grade areas in composite tumors did not show chromosome 3 alterations.

Conclusions:

  • Loss of BRM expression is a frequent characteristic of poorly differentiated clear cell RCCs.
  • BRM loss is hypothesized to be involved in the de-differentiation process of clear cell RCC.
  • BRM expression status may be an important factor in clear cell RCC tumor progression.

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