"Altered TFE3 in Translocation Renal Cell Carcinoma Can Be Associated W" by Allison Kennedy, Hassan Kanaan et al.
 

Altered TFE3 in Translocation Renal Cell Carcinoma Can Be Associated With the Increased Lysosome Activity Indicated by CD68 Overexpression

Document Type

Conference Proceeding

Publication Date

3-2025

Publication Title

Laboratory Investigation

Abstract

Background: TFE3 regulates autophagy/lysosome function in normal cells and TFE3 gene alteration in variants of translocation renal cell carcinoma (tRCC) can enhance the activity of autophagy/ lysosome thus partially contributing to the enhanced metabolic capacity of tumor cell growth in tRCC. This study aimed to determine if various TFE3 genetic alterations lead to the overexpression of lysosome activity indicated by upregulating CD68 immunohistochemical (IHC) expression. Design: In the retrospective study (over past 7 years), four groups of cases were tested for TFE3 by fluorescence in situ hybridization (FISH): 3 TFE3-positive alveolar soft part sarcoma (ASPS) as positive controls (also positive for CD68), 7 other TFE3-negative sarcomas as negative controls, 6 tRCC with TFE3 alterations as study positive group, and 7 TFE3 negative other RCC as study negative group. IHC was performed for lysosomal marker CD68 (KP1 clone, prediluted,Ventana) on TFE3-altered tRCC. The staining intensity was graded from 0 to 3+. Results: The age of tRCC patients ranged from 6 to 70 years old (Table 1). There were five female patients and one male patient, consistent with dominant female patients with TFE3 associated tRCC due to TFE3 gene location in X chromosome. The TFE3 alterations included 1 rearrangements (Figure 1A), 1 rearrangement plus copy number gain (Figure 1B, arrows for copy gain), 3 copy number gains and 1 copy number loss. All six (6/6) tRCC cases showed positive TFE3 nuclear immnostaining (MRQ-37 clone, Cell Marque). All 6 tRCC stained moderately (2+) to strongly (3+) positive for CD68 in the cytoplasm of the tumor cells, compatible with CD68 location in lysosome (Figure 1C-1D). Conclusions: Our data indicate that the changes of TFE3 can range from rearrangements to copy number variations. The combination of FISH and IHC for CD68 offers valuable insight into tumor biology, supporting the view that TFE3 alterations are linked to enhanced lysosome activity. These findings also reinforce the importance of FISH for diagnosing TFE3-altered tRCC.

Volume

105

Issue

3 Suppl

First Page

53

Comments

114th Annual Meeting of the United States and Canadian Academy of Pathology (USCAP), March 22-27, 2025, Boston, MA

Last Page

53

DOI

10.1016/j.labinv.2024.103057

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