Molecular Heterogeneity of Xp11.2 Translocation Renal Cell Carcinoma: The Correlation Between Split Signal Pattern in FISH and Prognosis

Abstract

Purpose

Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a distinct subtype of renal cell carcinoma (RCC) characterized by chromosomal translocations involving TFE3 gene. TFE3 break-apart fluorescence in situ hybridization (FISH) assay is an effective tool to diagnose Xp11.2 tRCC. The aim of this study is to evaluate the correlation between split signal pattern in FISH and the clinicopathological characteristics of Xp11.2 tRCC.

Patients and Methods

We reviewed 2037 RCC patients who underwent partial nephrectomy or radical nephrectomy from January 2007 to March 2020 in our institution. Forty-nine cases were diagnosed as Xp11.2 tRCC and their split signal patterns were evaluated. X-tile software was used to determine the optimal cut-off value of the percentage of split signal in FISH. Kaplan–Meier analysis and Cox regression analysis were performed to assess the relationship between signal pattern of FISH and the prognosis.

Results

Among the 49 patients, 13 patients and 36 patients were classified into high and low split signal group, respectively. Nine cases showed extra amplification signal pattern and 40 cases showed typical translocation signal pattern. Multivariate analysis demonstrated that high percentage of split signal and amplification signal pattern were the independent predictors for progression-free survival (PFS) whereas only pT stage was associated independently with overall survival (OS).

Conclusion

Xp11.2 tRCC cases with high percentage of split signals or amplification signal pattern may have a worse outcome, and the two indicators need to be highlighted in clinical practice.

Keywords:

• Xp11.2 translocation renal cell carcinoma
• TFE3
• FISH
• amplification
• prognosis

Acknowledgments

The authors thank Xiaogong Li, Gutian Zhang (Department of Urology, Nanjing Drum Tower Hospital) for providing patient information. We also thank Jun Yang and Ming Chen (Department of Pathology, Nanjing Drum Tower Hospital) for providing technical assistance.

Abbreviations

Xp11.2 tRCC, Xp11.2 translocation renal cell carcinoma; TFE3, transcription factor E3; WHO, World Health Organization; MiT, microphthalmia; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; %TFE3 split signals, the percentage of TFE3 split signals; AJCC, American Joint Committee on Cancer, ISUP, International Society of Urological Pathology; OS, overall survival; PFS, progression-free survival; SSC, sodium saline citrate; DAPI, 4,6-diamidino-2-phenylindole; SDHB, succinate dehydrogenase B; CNAs, copy number alterations; aCGH, array comparative genomic hybridization.

Data Sharing Statement

The dataset analyzed during the current study is not publicly available but is available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

This study was approved by the Ethics Committee of Nanjing Drum Tower Hospital and was performed in accordance with the standards of the Declaration of Helsinki. Written informed consent was not required because this was a retrospective study and all data were anonymized.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed on the journal to which the article will be submitted; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflict of interest in this work.