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.

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusions: Clinical Features, Treatments and Prognosis

“…Since being recognized as a distinct entity by the World Health Organization (WHO) in 2004 [1], Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) has attracted broad attention [2–5]. The term of Xp11.2 tRCC derived from several different chromosomal translocations of Xp11.2 breakpoints and formatting of TFE3 fusion gene, which resulted in a significant overexpression of TFE3 protein in tumor cells.…”

“…Although immunohistochemical staining for TFE3 (TFE3-IHC) serves as the basic method for the diagnosis of Xp11.2 tRCC, numerous reports have shown that TFE3-IHC has fairly high false-positive rates and low predictive values, which results in misdiagnoses in patients [4, 9–11]. To date, TFE3 break-apart fluorescence in situ hybridization (FISH) is regarded as the best method to diagnose Xp11.2 tRCC due to its advantages of high sensitivity and specificity [2, 12–15]. In the current study, 34 cases of Xp11.2 tRCC were diagnosed using a TFE3 break-apart FISH probe.…”

“…Despite its low incidence, Xp11.2 RCC is more harmful than conventional RCC because the majority of patients present at advanced stages and invasive clinical courses [2–5, 16]. Surgical treatment, especially radical nephrectomy (RN), remains the most common strategy to treat Xp11.2 tRCC.…”

Rapid development and recurrence of translocation renal cell carcinoma

“…False positive and negative rates for translocation RCC with this modality have been reported as 6.7% and 4.3%, respectively 5. Fluorescence in situ hybridisation assay may be more sensitive and specific4 but is less widely used.…”

“…However, no published algorithms exist for this uncommon neoplastic entity, with treatment being guided by contemporary management of clear cell RCC and literature reviews. As for other RCC subtypes, surgical resection remains the mainstay of treatment for non-metastatic translocation RCC 5. While radical nephrectomy is thought to offer greatest cancer-free survival rates, partial nephrectomy has been successfully performed in a series of four patients with 3 years’ follow-up 3.…”