Clinical and pathological heterogeneity of four common fusion subtypes in Xp11.2 translocation renal cell carcinoma

Wei Guo; Yiqi Zhu; Xiaohong Pu; Hongqian Guo; Weidong Gan

doi:10.3389/fonc.2023.1116648

Clinical and pathological heterogeneity of four common fusion subtypes in Xp11.2 translocation renal cell carcinoma

Front Oncol. 2023 Feb 3:13:1116648. doi: 10.3389/fonc.2023.1116648. eCollection 2023.

Authors

Wei Guo^{1

2}, Yiqi Zhu³, Xiaohong Pu⁴, Hongqian Guo³, Weidong Gan^{1

3}

Affiliations

¹ Department of Urology, Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, China.
² Department of Urology, Taizhou People's Hospital Affiliated to Nanjing Medical University, Taizhou, Jiangsu, China.
³ Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
⁴ Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

Abstract

Background: Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a group of rare and highly heterogeneous renal cell carcinoma (RCC). The translocation involving TFE3 and different fusion partners lead to overexpression of the chimeric protein. The purpose of this study is to explore the clinicopathological features of Xp11.2 tRCC with four common fusion subtypes.

Methods: We screened out 40 Xp11.2 tRCC patients from January 2007 to August 2021 in our institution. The diagnosis was initially confirmed by TFE3 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assay and their fusion partners were verified by RNA sequencing. Then the 40 cases were divided into two groups (DBHS family and non-DBHS family group) and a clinical comparison among the four common fusion subtypes was performed.

Results: Among the 40 cases, 11 cases with SFPQ-TFE3 gene fusion and 7 cases with NONO-TFE3 gene fusion were classified in DBHS group, the remaining cases with ASPL-TFE3 (11 cases) or PRCC-TFE3 (11 cases) gene fusion were classified in non-DBHS group. Lymph node (LN) metastasis (P=0.027) and distant metastasis (P=0.009) were more common seen in non-DBHS family group than DBHS family group and cases in DBHS family group have better progressive-free survival (PFS) (P=0.02). In addition, ASPL-TFE3 fusion was associated with worse outcome (P=0.03) while NONO-TFE3 fusion (P=0.04) predicted a better prognosis.

Conclusions: Different fusion partner genes may play a functional role in various morphology, molecular and biological features of Xp11.2 tRCCs. The impact of fusion partners on clinical characteristics of Xp11.2 tRCCs deserves further exploration.

Keywords: DBHS family; FISH; TFE3; Xp11.2 translocation renal cell carcinoma; prognosis.

Grants and funding

This research was supported by the Project of Invigorating Health Care through Science, Technology and Education, Jiangsu Provincial Key Medical Discipline (Laboratory) (ZDXKB2016014) and Beijing Ronghe Medical Development Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.