Varieties of altered TFE3 can occur in MiT-family-related renal cell carcinomas

In TFE3 translocation renal cell carcinoma (RCC), rearrangements involving the TFE3 gene can lead to overexpression of the TFE3 transcription factor. This upregulation increases lysosomal activity and autophagy, which in turn contributes to tumor cell proliferation. Although TFE3 translocation RCC is one of the more extensively studied RCC subtypes, other genetic abnormalities, such as gene copy number alterations, may also play a role in disease development. Accordingly, this study aimed to more precisely categorize TFE3-altered RCC variants using fluorescence in situ hybridization (FISH), while also evaluating their histopathological characteristics and clinical behavior.

In this retrospective study spanning the past 9 years, 16 cases of renal cell carcinoma (RCC) were examined for TFE3 gene alterations using FISH. The cohort was divided into two groups: TFE3-altered RCC cases as the positive group (n = 6) and TFE3-negative RCC cases as the negative group (n = 10). TFE3 alterations, tumor pathology, and clinical outcomes were systematically evaluated.

The age of patients with TFE3-altered RCC ranged from 6 to 70 years old. There were five female patients and one male patient, which is consistent with the known female predominance of this RCC subtype. The TFE3 alterations observed in this cohort included: TFE3 gene rearrangement (n = 1), TFE3 gene rearrangement with copy number gain (n = 1), copy number gain of intact TFE3 gene (n = 3), and copy number loss of TFE3 gene (n = 1). Clinical outcomes varied, with some patients experiencing poor prognoses, including the development of distant metastases.

Our data show that TFE3 alterations in RCC span a range of genetic events, from gene rearrangements to copy number variations, as determined by FISH. These TFE3-altered RCCs in adults may be associated with unfavorable outcomes, underscoring the value of FISH in both diagnosing and refining our understanding of TFE3-altered RCC.