TFE3 gene rearrangement and protein expression contribute to a poor prognosis of renal cell carcinoma

Junyi Lin; Zhuang Tang; Chengjunyu Zhang; Wen Dong; Yeqing Liu; Hao Huang; Hao Liu; Jian Huang; Tianxin Lin; Xu Chen

doi:10.1016/j.heliyon.2023.e16076

TFE3 gene rearrangement and protein expression contribute to a poor prognosis of renal cell carcinoma

Heliyon. 2023 May 6;9(5):e16076. doi: 10.1016/j.heliyon.2023.e16076. eCollection 2023 May.

Authors

Junyi Lin^{1

2}, Zhuang Tang^{1

3}, Chengjunyu Zhang^{1

3}, Wen Dong^{1

3

4}, Yeqing Liu⁵, Hao Huang^{1

3}, Hao Liu^{1

3}, Jian Huang^{1

3

4}, Tianxin Lin^{1

3

4}, Xu Chen^{1

3

4}

Affiliations

¹ Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China.
² Department of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
³ Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, China.
⁴ Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou, Guangdong, 510120, China.
⁵ Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China.

Abstract

Background: TFE3-rearranged renal cell carcinoma (TFE3-rearranged RCC) is a type of kidney cancer with a low incidence, with no consensus about whether it has a worse prognosis than clear cell renal cell carcinoma (ccRCC). This study attempted to elucidate the impact of TFE3-rearranged RCC by analyzing its clinical features and prognosis.

Methods: Patients treated in Sun Yat-sen Memorial Hospital (SYSMH) who were suspected to be diagnosed with TFE3-rearranged RCC were divided into two groups, TFE3-rearranged RCC and ccRCC with positive TFE3 protein expression on immunohistochemistry [TFE3(+) ccRCC], by dual-color, break-apart fluorescence in situ hybridization (FISH). After balancing the baseline characteristics with TFE3(+) ccRCC using the propensity score matching (PSM) method in a ratio of 2, we selected patients diagnosed with ccRCC with negative TFE3 protein expression on immunohistochemistry [TFE3(-) ccRCC]. The impact of TFE3 gene rearrangement and protein expression on renal cell carcinoma was determined by feature comparison with a nonparametric test and survival analysis with the Kaplan‒Meier method.

Results: Among 37 patients suspected of having TFE3-rearranged RCC, 13 patients were diagnosed with TFE3-rearranged RCC, and 24 patients had TFE3(+) ccRCC. The recurrence and new metastasis of TFE3-rearranged RCC was relatively common, even if the tumor stage was early at the first diagnosis. Through feature comparison and survival analysis, we found that TFE3-rearranged RCC was quite similar to TFE3(+) ccRCC. Compared with TFE3(-) ccRCC, TFE3(+) ccRCC tended to have a larger tumor diameter (P = 0.011), higher neutrophil/lymphocyte ratio (NLR) (P = 0.017) and metastatic potential (P = 0.022), and worse overall survival (OS) (P = 0.043) and PFS (P = 0.016). The survival analysis showed that TFE3-rearranged RCC had a worse PFS than ccRCC (P = 0.002), and TFE3(+) RCC had a worse PFS than TFE3(-) RCC (P = 0.001). According to the stratification system based on the combination of TFE3 and lymphovascular invasion (LVI), we further found that the prognosis from good to poor was TFE3(-) LVI(-), TFE3(+) LVI(-), TFE3(+) LVI(+) and TFE3(-) LVI(+), with statistically significant differences in both OS (P = 0.001) and PFS (P < 0.001). In addition, we also reported two cases with poor prognosis, of which one was TFE3-rearranged RCC and the other was TFE3(+) ccRCC.

Conclusions: This is a novel finding that both FISH confirmed TFE3 gene rearrangement-mediated TFE3-rearranged RCC and IHC confirmed positive TFE3 protein expression [TFE3(+)] contribute to a poor prognosis in RCC, suggesting more active treatment and careful follow-up for TFE3(+) RCC patients. The combination of TFE3 and LVI may be a new risk stratification system for RCC.

Keywords: LVI; Prognosis; Renal cell carcinoma; TFE3; TFE3-Rearranged RCC.