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

Abstract

BackgroundXp11.2 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.MethodsWe 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.ResultsAmong 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.ConclusionsDifferent 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.

Renal cell carcinoma associated with Xp11.2 translocation/transcription factor E3 gene fusion: A case report and literature review

“…Xp11.2 translocation RCC with TFE3 gene fusion is a rare subtype of RCC (5). It occurs due to a gene fusion between the TFE3 gene on the Xp11.2 chromosome and one of six different fusion partners (6).…”

“…IHC typically shows minimal reactivity to CK7 or vimentin (31). Overexpression of the TFE3 protein is observed due to translocation, and studies have demonstrated the sensitivity (97.5%) and specificity (99.6%) of TFE3 protein expression in diagnosing Xp11.2 translocation RCC (5,31). Therefore, TFE3 protein expression detected by IHC is the most commonly utilized auxiliary diagnostic technique in clinical practice (32).…”

Racial Disparities and Molecular Insights in Translocation Renal Cell Carcinoma: Advancing Understanding and Treatment Approaches

“… 6-8 Notably, different binding partners of TFE3 and TFEB have been associated with distinct clinicopathologic features and clinical behaviors. 9 Given the rarity of this subtype, there is a relative scarcity of research elucidating the molecular drivers of tRCC, resulting in a lack of targeted therapy regimens specific to tRCC.…”