Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population

Abstract

This study aimed to assess the utility of transcription factor E3 (TFE3) break-apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.2 RCC and non-Xp11.2 RCC. 76 pathologically suspected Xp11.2 RCCs were recruited from our institution. Both TFE3 immunohistochemistry (IHC) and TFE3 FISH assay were performed for the entire cohort. The progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. FISH analysis confirmed 30 Xp11.2 RCCs, including 28 cases with positive TFE3 immunostaining and 2 cases with negative immunostaining. The false-positive and false-negative rates were 6.7% (2/30) and 4.3% (2/46), respectively, for TFE3 IHC compared with FISH assay. Xp11.2 RCC was significantly associated with higher pathological stage and Fuhrman nuclear grade compared with non-Xp11.2 RCC (P < 0.05). The median PFS and OS for TFE3 FISH-positive group were 13.0 months (95% CI, 8.4-17.6 months) and 50.0 months (95% CI, 27.6-72.4 months), respectively, while the median PFS and OS had not been reached for TFE3 FISH-negative group. In conclusion, TFE3 break-apart FISH assay is a highly useful and standard diagnostic method for Xp11.2 RCC. Adult Xp11.2 RCC is clinically aggressive and often presents at advanced stage with poor prognosis.

Figure 1. Representative images of TFE3 immunohistochemical staining and microscopic appearance for Xp11.2 RCC.

(A) Showed strong nuclear expression of TFE3 (×200); (B) Showed negative expression of TFE3 (×200); (C) Showed microscopic appearance of an Xp11.2 translocation renal cell carcinoma comprised voluminous, clear cytoplasm with bulging cell borders and small to moderately size nuclei and psammoma bodies (arrow) (H&E, ×200); (D) Showed microscopic appearance of an Xp11.2 translocation renal cell carcinoma with nested structures populated by clear to slightly eosinophilic cells with numerous cytoplasm and round nuclei with prominent nucleoli (H&E, ×200). TFE3, transcription factor E3; RCC, renal cell carcinoma; H&E, hematoxylin and eosin.

Figure 2. Representative images of the TFE3 break-apart probe assay.

(A) Demonstrate a pair of split red and green signals (red and green arrows) as well as a normal fused hybridization signals (yellow arrows) in a female patient, indicating the translocation of one X chromosome and a normal another (×1000); (B) Demonstrate a pair of split red and green signals (red and green arrows) in a male patient, indicating the translocation of the only X chromosome (×1000); (C) Demonstrate two normal fusion signals (yellow arrows) in a female patient (×1000); (D) Demonstrate one normal fusion red-green signals (yellow arrows) in a male patient (×1000). TFE3, transcription factor E3.

Figure 3

Kaplan-Meier analysis for progression-free survival (A) and overall survival (B) in the entire cohort according to TFE3 FISH analysis. TFE3, transcription factor E3; FISH, fluorescence in situ hybridization.