ABSTRACT
Objective:To investigate the clinicopathological features and prognosis of adult Xp11.2/TFE3 gene fusion-associated renal cell carcinoma (TFE3 RCC).Methods:The clinical data of 55 patients with TFE3 RCC admitted to the First Affiliated Hospital of Zhejiang University Medical College from January 2013 to February 2021 were retrospectively analyzed, including 26 males and 29 females. The patients’ mean age was (40.6 ± 14.7) years. The median tumor size was 4.0 (1.9-20.0) cm. Tumors were located in the left kidney in 30 cases (54.5%) and the right kidney in 25 cases (45.5%). Preoperative imaging assessment was well-circumscribed in 41 patients (74.5%) and ill-defined in 14 patients (25.5%). There were 2 cases of regional lymph node metastasis and 2 cases of distant metastasis, including 1 case of lung metastasis and 1 case of bone metastasis. Preoperative staging included stage I in 38 patients (69.1%), stageⅡ in 5 patients (9.1%), stage Ⅲ in 9 patients (16.4%), and stageⅣin 3 patients (5.5%). Nephron-sparing surgery was performed in 31 patients (56.4%) and radical nephrectomy in 24 patients (43.6%). Progression-free survival curves were plotted by the Kaplan-Meier method and analyzed by the log-rank test. Cox proportional hazards regression model was applied for multivariate analysis of factors influencing progression-free survival.Results:Postoperative pathological stage included pT 1 in 41 patients (74.5%), pT 2 in 5 patients (9.1%), pT 3 in 8 patients (14.5%), and pT 4 in 1 patient (1.8%). Four patients (7.3%) had N 1 stage and 2 (3.6%) had M 1 stage. After immunohistochemical analysis, TFE3 showed diffuse strong positive reaction in 55 patients, cathepsin K positive in 36 patients (65.5%), CD10 positive in 48 patients (87.3%), CK7 positive in 7 patients (12.7%), CA-IX positive in 2 patients (3.6%), and PAX8 positive in 35 patients (63.6%). Two cases were tested by fluorescent in situ hybridization (FISH), and the results were positive. The proportion of nuclei with mitotic signals was 40% and 30%, respectively. The median follow-up time was 27 (3-96) months. The results of survival analysis showed that the 3-year and 5-year progression-free survival rates were 80.0% and 64.0%, respectively. The results of univariate analysis showed that tumor size ( P = 0.009), pT stage ( P<0.001), regional lymph node invasion ( P = 0.003), and surgical approach ( P = 0.006) were associated with the prognosis of TFE3 RCC patients. Multivariate analysis of the Cox model was performed on significant univariate factors, and its results showed that pT stage ( HR=4.824, 95% CI 1.129-20.604, P=0.034) and regional lymph node invasion ( HR=5.522, 95% CI 1.066-28.611, P = 0.042) were independent prognostic factors for progression-free survival in TFE3 RCC patients. The results of stratified analysis showed that for patients with pT 1 disease, the effect of surgical approach on the prognosis of patients was not statistically significant ( P=0.091). The 3-year progression-free survival rates for nephron-sparing surgery and radical nephrectomy were 94.7% and 81.5%, respectively. Conclusions:Given that TFE3 RCC imaging studies often lack characteristic features, diagnosis mainly relies on immunohistochemical analysis and FISH tests. Most of the patients with TFE3 RCC have a better prognosis after surgical treatment. However, pT stage and regional lymph node invasion were prognostic factors in patients with TFE3 RCC.