RRC ID 73815
著者 Takamatsu D, Kohashi K, Kiyozawa D, Kinoshita F, Ieiri K, Baba M, Eto M, Oda Y.
タイトル TFE3-immunopositive papillary renal cell carcinoma: A clinicopathological, immunohistochemical, and genetic study.
ジャーナル Pathol Res Pract
Abstract It is possible that PRCCs may still contain a variety of unknown histologic subtypes. Some PRCCs express high expression of TFE3 protein without TFE3 gene rearrangement, but no reports have investigated the significance of this. Here we attempted to examine clinicopathological and molecular significance of the TFE3-immunopositive PRCC. We reviewed the histology and immunohistochemistry in 58 PRCCs. TFE3 immunoexpression was recognized in 7 cases. Because TFE3 immunostaining shows false-positive, to ensure the integrity of TFE3 immunostaining, the immunostaining was performed under strict control of internal controls and western blotting was performed on 2 positive cases and 5 negative cases, and differences in protein expression between two groups were confirmed. Significant immunohistochemical expressions of autophagy/lysosome proteins were observed in TFE3-positive group. No TFE3 gene arrangement was detected in all positive cases by fluorescence in situ hybridization. Whole-exome sequencing was performed on 6 TFE3-positive and 2 TFE3-negative cases. Gain of chromosome 7 was found in five of 6 TFE3-positive cases (83%). TFE3-positive group was correlated significantly with higher pTstage, cNstage, WHO/ISUP nuclear grade, and decreased OS. TFE3-immunopositive PRCC group had a poorer prognosis than TFE3-negative PRCC group and showed correlation with expressions of autophagy/lysosome proteins, suggesting that enhancement of autophagy/lysosome function drives an environment of energy metabolism that is favorable for cancer. It is necessary to recognize that there is TFE3-immunopositive group without TFE3 gene rearrangement within PRCC. Because of its aggressive biological behaviour, TFE3 can act as a biomarker in PRCC; moreover, autophagy-inhibiting drugs may have therapeutic effects on TFE3-immunopositive PRCC.
巻・号 242
ページ 154313
公開日 2023-2-1
DOI 10.1016/j.prp.2023.154313
PII S0344-0338(23)00013-4
PMID 36669395
MeSH Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics Carcinoma, Renal Cell* / pathology Humans In Situ Hybridization, Fluorescence Kidney Neoplasms* / pathology Transcription Factors / genetics Translocation, Genetic
IF 2.05
リソース情報
ヒト・動物細胞 S-TFE(RCB4699)