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Test ID: TFE3    
Alveolar Soft Part Sarcoma (ASPS)/Renal Cell Carcinoma (RCC), Xp11.23 (TFE3), FISH, Tissue

Useful For Suggests clinical disorders or settings where the test may be helpful

Aids in the diagnosis of alveolar soft-part sarcoma or renal cell carcinoma variant when used in conjunction with an anatomic pathology consultation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Alveolar soft-part sarcoma (ASPS) is a rare malignant tumor typically occurring in patients in their 20s to 30s within the muscle and deep tissues of the extremities. ASPS is slow growing and refractory to chemotherapy with a propensity to metastasize. Prolonged survival is possible even with metastasis, although the long-term disease-related mortality rate is high. ASPS is characterized by a translocation that results in fusion of TFE3 on chromosome Xp11.2 with ASPSCR1 (also called ASPL or RCC17) on chromosome 17q25.3.(1,2) Both balanced and unbalanced forms (loss of the derivative X chromosome) of the translocation have been observed.(2,3)

 

Another tumor, a rare subset of papillary renal cell carcinoma (RCC) with a distinctive pathologic morphology, has rearrangements of TFE3 with ASPSCR1 or other fusion partner genes.(1,4,5) This tumor predominantly affects children and young adults, presents at an advanced stage but with an indolent clinical course, and is a distinct entity in the World Health Organization classification.(6) Typically a balanced form of the translocation is present in the RCC variant. An assay to detect rearrangement of TFE3 is useful to resolve diagnostic uncertainty in these tumor types, as immunohistochemistry for TFE3 is not reliable.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

A neoplastic clone is detected when the percent of nuclei with the abnormality exceeds the established normal cutoff for the TFE3 probe set. A positive result of TFE3 rearrangement is consistent with a diagnosis of alveolar soft-part sarcoma (ASPS) or renal cell carcinoma (RCC) variant. A negative result suggests that TFE3 is not rearranged, but does not exclude the diagnosis of ASPS or RCC variant.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the FDA and it is best used as an adjunct to existing clinical and pathologic information.

Supportive Data

FISH analysis was performed on 25 normal samples from each gender (50 total), 12 tumor samples classified by a pathologist (10 alveolar soft-part sarcoma: ASPS; 2 renal cell carcinoma: RCC variant), and 9 tumors in the differential diagnosis in a blinded manner using standard sample processing techniques and FISH methodology.

 

No rearrangements of TFE3 were identified in 50 normal patient specimens or 9 tumor mimics. Of the 10 ASPS cases, 4 did not have a rearrangement, 2 had a balanced TFE3 separation, and 4 had an atypical TFE3 separation (presence of 2 normal X chromosomes and the derivative 17, but loss of the derivative X). This atypical rearrangement was confirmed using a TFE3/ASPSCR1 probe set. Of the 2 diagnostic RCC cases, 1 was normal and 1 had an atypical TFE3 separation, but reflex testing with the TFE3/ASPSCR1 probe was not possible due to insufficient sample.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Zhong M, De Angelo P, Osborne L, et al: Dual-color break-apart FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of Xp11 translocation renal cell carcinoma and alveolar soft part sarcoma. Am J Surg Pathol 2010;34(6):757-766

2. Ladanyi M, Lui MY, Antonescu CR, et al: The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 2001;20:48-57

3. Williams A, Bartle G, Vaiyapuri SP, et al: Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: Useful diagnostic tools in cases with unusual histologic features. Virchows Arch 2011;458:291-300

4. Ross H, Argani P: Xp11 translocation renal cell carcinoma. Pathology 2010;42(4):369-373

5. Armah HB, Parwani AV: Xp11.2 translocation renal cell carcinoma. Arch Pathol Lab Med 2010;134:124-129

6. WHO Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs In IARC WHO Classification of Tumours. Edited by JN Eble, et al. Lyon: IARC Press, 2004, pp 37-38