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Journal of Peking University (Health Sciences) ›› 2025, Vol. 57 ›› Issue (4): 650-661. doi: 10.19723/j.issn.1671-167X.2025.04.004

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Clinicopathological features and survival analysis of TFE3-rearranged renal cell carcinoma with venous tumor thrombus

Zhanyi ZHANG1, Min LU2,3, Yuehao SUN1, Jinghan DONG1, Xiaofei HOU1, Chunlei XIAO1, Guoliang WANG1, Xiaojun TIAN1, Lulin MA1, Hongxian ZHANG1, Shudong ZHANG1,4,*()   

  1. 1. Department of Urology, Peking University Third Hospital, Beijing 100191, China
    2. Department of Pathology, Peking University Third Hospital, Beijing 100191, China
    3. Department of Pathology, Peking University School of Basic Medical Sciences, Beijing 100191, China
    4. Cancer Center, Peking University Third Hospital, Beijing 100191, China
  • Received:2025-02-28 Online:2025-08-18 Published:2025-08-02
  • Contact: Shudong ZHANG
  • Supported by:
    the National Natural Science Foundation of China(82273389); the Beijing Natural Science Foundation(7232212)

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Abstract:

Objective: To review the clinicopathological features of TFE3-rearranged renal cell carcinoma (TFE3-RCC) with venous tumor thrombus (VT) (TFE3-VT), to explore treatment strategies and to prognostic characteristics, and to provide diagnostic and therapeutic references for TFE3-VT patients. Methods: Patients who underwent surgery at Department of Urology, Peking University Third Hospital from January 2013 to January 2024 were enrolled, including three cohorts: Pathologically confirmed TFE3-VT patients, TFE3-RCC patients without VT (TFE3-non-VT), and non-TFE3-rearranged renal cell carcinoma patients with VT (non-TFE3-VT). Clinical history, imaging data, pathological data, and follow-up records were collected. Primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. (1) Baseline characteristics were compared between the TFE3-VT and TFE3-non-VT patients. Normally distributed continuous variables were expressed as mean±SD and compared using Student's t-test; non-normally distributed variables were expressed as M (P25, P75) and analyzed with Mann-Whitney U test; categorical variables were described as frequency and percentage [n (%)] and compared by χ2 test or Fisher's exact test. (2) Clinical history, radiological presentations, surgical data, and histopathological features of the TFE3-VT patients were comprehensively characterized. (3) Survival analysis was performed for the TFE3-VT patients. Follow-up data of the TFE3-VT patients were described in detail, and their survival outcomes were compared with the TFE3-non-VT and non-TFE3-VT patients. When compared with the TFE3-non-VT counterparts, Kaplan-Meier method was used to generate PFS and OS curves among: (1) the TFE3-RCC patients across clinical stages Ⅰ-Ⅳ; (2) TFE3-VT versus TFE3-non-VT cohorts; (3) stage Ⅲ subgroups of the TFE3-VT and TFE3-non-VT patients. Intergroup survival differences were statistically evaluated using Log-rank tests. For comparisons with the non-TFE3-VT patients, a 1 : 1 propensity score matching (PSM) was implemented to balance baseline characteristics between the two cohorts. Post-matching Kaplan-Meier curves were generated to compare PFS and OS between the matched groups, with Log-rank tests employed to determine statistical significance of survival disparities. All statistical analyses were conducted with R software (v 4.2.3), and two-tailed P < 0.05 was considered statistically significant. Results: The study included 45 TFE3-RCC patients: 13 TFE3-VT and 32 TFE3-non-VT cases. Additionally, 523 non-TFE3-VT patients were enrolled. Among the 13 TFE3-VT patients, 9 were female (69.2%) and 4 male (30.8%), with a mean age of (37.9±14.4) years, mean BMI of (22.2 ± 3.5) kg/m2, median age-adjusted Charlson comorbidity index (aCCI) of 1.0 (0.0, 1.0), and preoperative creatinine level of (75.3±15.9) μmol/L; tumors were located in the left kidney in 7 patients (53.8%) and right kidney in 6 (46.2%); preoperative distant metastasis (M1 stage) was present in 6 patients (46.2%), while 7 (53.8%) showed no metastasis; VT distribution by Mayo level comprised 7 cases (53.8%) at level 0, 1 case each at levels Ⅰ and Ⅳ (7.7% respectively), and 2 cases each at levels Ⅱ and Ⅲ (15.4% respectively); surgical approaches comprised open surgery (n=2, 15.4%), laparoscopic surgery (n=6, 46.1%), and robot-assisted laparoscopic surgery (n=5, 38.5%); mean operative time was (273±79) min, and intraoperative blood loss was (722±570) mL; mean maximum tumor diameter was (10.8±2.4) cm. All the 13 patients underwent TFE3 protein immunohistochemistry (IHC) staining, with 7 confirmed by fluorescence in situ hybridization (FISH). Tumor recurrence or metastasis occurred in 11 patients (84.6%), and 9 (69.2%) patients died during follow-up. Median PFS was 4 months (1 year PFS rate: 31%), and median OS was 13 months (1 year OS rate: 54%). Survival analysis of 45 TFE3-RCC patients revealed statistically significant differences in PFS and OS across all the clinical stages (P < 0.001). The TFE3-VT patients exhibited significantly worse PFS and OS than the TFE3-non-VT patients (P < 0.001), with persistent significance in stage Ⅲ subgroup analysis (P < 0.05). After PSM, TFE3-VT patients showed significantly inferior PFS compared with non-TFE3-VT (P=0.01), though no significant difference was shown between the OS curves (P=0.11). Conclusion: TFE3-VT predominantly occurs in young females with frequent preoperative metastases. Strongly-positive staining of TFE3 protein in IHC staining and red-green split signals in FISH tests are reliable diagnostic markers. TFE3-VT patients exhibit inferior survival compared with TFE3-non-VT patients and earlier progression than non-TFE3-VT patients.

Key words: Renal cell carcinoma, TFE3 gene, Venous tumor thrombus, Immunohistochemical staining, Fluorescence in situ hybridization

CLC Number: 

  • R737.11

Table 1

Baseline characteristics of 45 TFE3 -RCC patients with or without VT"

Items TFE3-VT (n=13) TFE3-non-VT (n=32) P value
Age/years, ${\bar x}$±s 37.9 ±14.4 36.0 ±13.1 0.662
Gender, n (%) 0.638
  Male 4 (30.8) 14 (43.8)
  Female 9 (69.2) 18 (56.2)
BMI/(kg/m2), ${\bar x}$±s 22.2 ±3.5 24.8 ±3.4 0.023*
aCCI, M (P25, P75) 1.0 (0.0, 1.0) 0.0 (0.0, 1.0) 0.376
ASA level, n (%) 0.840
  1 7 (53.8) 20 (62.5)
  2 6 (46.2) 12 (37.5)
Cr/(μmoL/L), ${\bar x}$±s 75.3 ±15.9 75.6±16.6 0.953
Laterality, n (%) 0.924
  Left 7 (53.8) 15 (46.9)
  Right 6 (46.2) 17 (53.1)
Surgical approach, n (%) < 0.001*
  Laparoscopic 2 (15.4) 23 (71.9)
  Open 6 (46.1) 0 (0.0)
  Robotic 5 (38.5) 9 (28.1)
Operative time/min, M (P25, P75) 292.0 (194.0, 320.0) 138.0 (109.8, 167.8) < 0.001*
Blood loss/mL, M (P25, P75) 600.0 (300.0, 1 100.0) 40.0 (17.5, 100.0) < 0.001*
RBC transfusion/mL, M (P25, P75) 0.0 (0.0, 600.0) 0.0 (0.0, 0.0) < 0.001*
Clavien-Dindo level, n (%) 0.031*
  0-Ⅰ 9 (69.2) 31 (96.9)
  Ⅱ 4 (30.8) 1 (3.1)
Postoperative hospital stays/d, M (P25, P75) 9.0 (6.0, 14.0) 6.0 (5.0, 6.0) 0.009*
Tumor diameter/cm, M (P25, P75) 10.3 (9.6, 12.0) 4.4 (3.2, 6.5) < 0.001*
pT stage, n (%) < 0.001*
  pT1 0 (0.0) 23 (71.9)
  pT2 0 (0.0) 4 (12.5)
  pT3 11 (84.6) 5 (15.6)
  pT4 2 (15.4) 0 (0.0)
N1 stage, n (%) 5 (38.5) 3 (9.4) 0.060
M1 stage, n (%) 6 (46.2) 0 (0.0) < 0.001*
Clinical tumor stage, n (%) < 0.001*
  Stage Ⅰ 0 (0.0) 22 (68.8)
  Stage Ⅱ 0 (0.0) 4 (12.5)
  Stage Ⅲ 6 (46.2) 6 (18.8)
Stage Ⅳ 7 (53.8) 0 (0.0)
Nuclear grade, n (%) 0.003*
  Ⅰ-Ⅱ 0 (0.0) 17 (53.1)
  Ⅲ-Ⅳ 13 (100.0) 15 (46.9)
Sarcomatoid differentiation, n (%) 2 (15.4) 1 (3.1) 0.404

Table 2

Clinical history, radiological tumor characteristics and surgical data of 13 TFE3-VT patients"

Figure 1

Contrast-enhanced CT images from a left-sided TFE3 -rearranged renal cell carcinoma patient combined with Mayo level 0 renal vein thrombus (case 8) A, B, 9.4×9.6×9.5 cm mass was identified in the upper pole of the left kidney, the margin of the mass was well-defined; on non-contrast CT scan, the mass (yellow circle with dashed line) demonstrated heterogeneous soft tissue density (50-70 HU) with patchy areas of low density (30-40 HU); central punctate calcifications were observed within the lesion (white circle with solid line); the left renal vein was dilated (white arrow, axial plane). C, D, on contrast-enhanced CT imaging (arterial phase), the solid components of the mass showed marked heterogeneous enhancement (80-120 HU), while the cystic areas within the lesion exhibited no obvious enhancement; tumor thrombus was identified within the renal vein (white arrow), measuring approximately 3.7 cm in length (axial plane). E, F, on contrast-enhanced CT imaging (arterial phase), multiple fine septations were visible within the cystic areas and demonstrated enhancement (white arrow head); the perirenal fascia was compressed, and the lesion was in close proximity to the left adrenal gland and spleen; the left renal vein exhibited a filling defect and indicated tumor thrombus (white arrow); no significantly enlarged lymph nodes were seen (coronal plane)."

Table 3

Histopathological features of 13 TFE3-VT patients"

Figure 2

Pathological images from a left-sided TFE3-rearranged renal cell carcinoma patient with Mayo level Ⅱ inferior vena cava thrombus (case 9) A, Hematoxylin-Eosin staining (×200), tumor cells exhibit clear cytoplasm arranged in a sheet-like pattern; B, immunohistochemistry staining of PAX-8 (×200), staining of tumor cell nuclei was strongly positive for PAX-8; C, immunohistochemistry staining of TFE3 protein (×200), staining of tumor cell nuclei was strongly positive for TFE3, FISH-TFE3 showed red-green split signals (inset)."

Table 4

Postoperative therapy and survival outcomes of 13 TFE3 -VT patients"

Items Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7
Postoperative therapy TKI TKI TKI None TKI TKI TKI, ICI
Type of TKI Sunitinib, axitinib Sunitinib Sunitinib None Pazopanib NA Sunitinib, axitinib, anlotinib
Type of ICI None None None None None None Triprolizumab, bevacizumab (peritoneal perfusion)
Death + + + + + - +
Death reason Cancer NA Cancer Cancer Cancer None Cancer
OS/months 56 3 9 12 8 16 13
Progression + + + + + + +
Sites of tumor relapse or metastasis Lung, liver NA Abdominal wall, surgical region Lung, liver Liver Lung, liver Liver, peritoneum, omentum, retroperitoneal region
PFS/months 13 3 4 3 1 11 6
Items Case 8 Case 9 Case 10 Case 11 Case 12 Case 13
Postoperative therapy TKI TKI TKI TKI, radiotherapy, ICI None TKI, ICI
Type of TKI Sunitinib, axitinib Pazopanib Pazopanib Sunitinib, axitinib None Axitinib
Type of ICI None None None Pembrolizumab None Pembrolizumab
Death + + - - + -
Death reason Cancer Cancer None None Cancer None
OS/months 40 1 34 31 2 16
Progression + + + - + -
Sites of tumor relapse or metastasis Lung Liver, adrenal gland, abdominal wall Surgical region, cervical and mediastinal lymph nodes, lung None NA None
PFS/months 1 0 13 31 2 16

Figure 3

Kaplan-Meier curves of TFE3 -VT, TFE3 -non-VT, and non- TFE3 -VT A, B, progression free survival and overall survival curves of TFE3-RCC patients with different clinical tumor stage (2017 American Joint Committee on Cancer 8th version); C, D, progression free survival and overall survival curves of TFE3-VT and TFE3-non-VT patients; E, F, progression free survi-val and overall survival curves of stage Ⅲ TFE3 -VT and TFE3 -non-VT patients.; G, H, progression free survival and overall survival curves of TFE3 -VT and non-TFE3 -VT patients after 1 ∶ 1 propensity score matching. TFE3 -RCC, TFE3 -rearranged renal cell carcinoma; TFE3 -VT, TFE3 -rearranged renal cell carcinoma with venous tumor thrombus; TFE3 -non-VT, TFE3-rearranged renal cell carcinoma patients without VT; non-TFE3 -VT, non-TFE3 -rearranged renal cell carcinoma patients with VT."

Table 5

Distribution of matching factors before and after propensity score matching (PSM)"

Items Before PSM SMD After PSM SMD
TFE3-VT (n=13) non-TFE3-VT (n=523) TFE3-VT (n=13) non-TFE3-VT (n=13)
Age/years, n (%) 1.432 < 0.001
  ≤45 8 (61.5) 60 (11.5) 8 (61.5) 8 (61.5)
  >45-65 5 (38.5) 312 (59.7) 5 (38.5) 5 (38.5)
  ＞65 0 (0.0) 151 (28.9) 0 (0.0) 0 (0.0)
Gender, n (%) 0.857 < 0.001
  Male 4 (30.8) 367 (70.2) 4 (30.8) 4 (30.8)
  Female 9 (69.2) 156 (29.8) 9 (69.2) 9 (69.2)
M1 stage, n (%) 7 (53.8) 144 (27.5) 0.556 7 (53.8) 7 (53.8) < 0.001
Neoadjuvant therapy, n (%) 4 (30.8) 66 (12.6) 0.451 4 (30.8) 4 (30.8) < 0.001
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