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Soft Tissues: Alveolar soft part sarcoma with t(X;17)(p11;q25) ASPSCR1::TFE3

Written2007-07Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France
This article is an update of :
2001-08Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France

(Note : for Links provided by Atlas : click)


ICD-Topo C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE
ICD-Morpho 9581/3 Alveolar soft part sarcoma
Atlas_Id 5125
Phylum Soft Tissues::Alveolar soft part sarcoma
WHO/OMS Classification Soft Tissues
Other namesMalignant nonchromaffin paraganglioma
Malignant organoid granular cell myoblastoma

Clinics and Pathology

Embryonic origin The histogenesis of this tumour is still unknown, despite immunohistochemestry studies and electron microscopy. It may have a myogenic origin, and might be a variant of rhabdomyosarcoma.
Epidemiology Rare tumour: represents less than 1% of soft tissues sarcomas of adults and 1-2% of soft tissues sarcomas in children.
Occurs most often in the young adult, less frequently in children.
Median age is 20 yrs in female patients, and 30 yrs in male patients. More frequently, patients are females (ratio M/F is 2/3).
Clinics Involve the muscles and soft tissues, in particular those of the lower extremities (buttocks, thighs and legs). This represents more than half cases in the adults. It may also arise in the upper extremities, in the head and neck regions, especially in the child, but it can also have extra muscular localizations, such as the female genital tract, the trunk, the mediastinum, or the retroperitoneum.
Metastases are frequent. They occur mainly in lungs, bones, and brain.
Symptoms at diagnosis may be pain and/or swelling. Diagnosis is often retarded.
Pathology Well circumscribed tumours with a multinodular pattern, haemorrhagic and necrotic.
Microcopically, exhibits an alveoloar structure, the center of the alveolar space being formed by detachment of necrotic cells, and with surronding capillaries (there is a more solid pattern in children).
Cells are large, with abundant cytoplasm. Mitoses are rare.
Secretory process with the formation of cytoplasmic membrane-bound crystals (PAS+, diastase resistant) can often be seen with electron microscopy, a feature of great diagnostic value (they are pathognomic). These granules contain monocarboxylate transporter 1 ( MCT1)- CD147 complexes.
Immunochemistry: in general, alveolar soft part sarcomas are negative for neuroendocrin and epithelial markers, and often positive for vimentin, muscle-specific actin, and desmin. The strong nuclear staining of an anti C-term TFE3 can be used for diagnosis (although cytogenetics and/or molecular genetics are the most relevant tools for diagnosis).
To be noted is that a subset of renal cell carcinomas, the primary renal ASPSCR1-TFE3 tumour, share some morphological features with the alveolar soft part sarcoma (it may be a differential diagnosis); they also share a common genetic substratum.
Treatment Primary tumours: large surgical excision (a complete resection is of great importance) and radiation.
Metastases: chemotherapy, with or without radiation or surgery, depending on the number of metastases.
Evolution Slow growing tumour, but highly angiogenic, which favours metastases dissemination.
Metastases appear in more than half of the patients who presented without metastases at diagnosis (up to 70 % in one study); however, there is a long disease-free interval before appearence of metastases (median 6 yrs) in these patients.
Prognosis Relatively indolent clinical course. In one study, overall survival of adult patients without metastases reached 87% at 5 yrs, but that of adult patients with metastases at diagnosis was only 20% at 5 yrs, with a median survival of 40 mths. Pediatric cases had a better prognosis, with a 5 yrs survival of 80% for all cases included, reaching 91% in cases without metastases.
Median survival in patients without metastases at diagnosis was noted above 10 yrs in a large -but old (period 1923-1986)- study, and it may be expected that progress has been made. Due to the rarity of the disease and its long course, survival data are outdated.


t(X;17)(p11;q25) is found in all alveolar soft part sarcomas so far studied, but also in primary renal ASPSCR1-TFE3 tumours. In the case of alveolar soft part sarcoma, the chromosome rearrangement is found in an unbalanced form, as a der(17)t(X;17)(p11;q25), in 80% of cases;
the unbalanced form implicates:
1- the formation of a hybrid gene at the breakpoint, but also,
2- gain in Xp11-pter sequences, and loss of heterozygocity in 17q25-qter, with possible implications, although no clinical (including prognostic) nor pathological differences have so far been noted between balanced and unbalanced cases... but, again, the disease is rare, and cases with cytogenetic studies even rarer (about 25 cases).
Note: the t(X;17)(p11;q25) in primary renal ASPSCR1-TFE3 tumours is balanced in all known cases.

Genes involved and Proteins

Note Retention of heterozygocity in the tumours of female patients (i.e. a normal maternal X and a normal paternal X are present, in addition to the Xp11-pter involved in the translocation) has been noted in all (n=7) female cases studied, showing that the translocation occurred in G2 phase.
Gene NameTFE3 (transcription factor E3)
Location Xp11.23
Dna / Rna 8 exons
Protein Transcription factor; member of the basic helix-loop-helix family (b-HLH) of transcription factors primarily found to bind to the immunoglobulin enchancer muE3 motif.

Gene NameASPSCR1 (Alveolar soft part sarcoma critical region 1)
Location 17q25.3
Protein Contains an UBX domain, ASPSCR1 binds SLC2A4 (solute carrier family 2 (facilitated glucose transporter), member 4, also called GLUT4) endocytosed from the plasma membrane into vesicles. SLC2A4 is retained in the cell by ASPSCR1 in the absence of insulin. Insulin stimulates the release of retained SLC2A4 to exocytosis, allowing the rapid mobilization of glucose transporters to the cell surface.

Result of the chromosomal anomaly

Hybrid Gene
Description 5' ASPSCR1-3' TFE3; the reciprocal 5' TFE3 - 3' ASPSCR1 is most often absent. ASPSCR1 is fused in frame either to TFE3 exon 3 or to exon 4 (type 1 and type 2 fusions respectively).
Fusion Protein
Description 234 NH2 term amino acids from ASPSCR1, fused to the 280 or 315 C term amino acids from TFE3, including the activation domain, the helix-loop-helix, and the leucine zipper from TFE3.


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This paper should be referenced as such :
Huret, JL
Soft tissue tumors: Alveolar soft part sarcoma
Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):250-252.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Huret, JL. Soft tissue tumors: Alveolar soft part sarcoma. Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):296-297.

Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]


Translocations implicated (Data extracted from papers in the Atlas)

 t(X;17)(p11;q25) ASPSCR1/TFE3

External links

Mitelman database t(X;17)(p11;q25) [CaseList]     t(X;17)(p11;q25) [Transloc - MCList]   ASPSCR1/TFE3 Fusion - MCList]
arrayMap Topo ( C47,C49) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseASPSCR1/TFE3[MCList]    ASPSCR1 (17q25.3) TFE3 (Xp11.23)   t(X;17)(p11;q25)
TICdbASPSCR1/TFE3    ASPSCR1 (17q25.3) TFE3 (Xp11.23)
Other databaseThe Alliance against ASP Sarcoma
Other databaseCure Alveolar Soft Part Sarcoma International
Disease databaseSoft Tissues: Alveolar soft part sarcoma with t(X;17)(p11;q25) ASPSCR1::TFE3
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

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