Alveolar soft-part sarcomas.Structurally characteristic tumors of uncertain histogenesis

Christopherson, William M.; Foote, Frank W.; Stewart, Fred W.

doi:10.1002/1097-0142(195201)5:1<100::aid-cncr2820050112>3.0.co;2-k

Cited by 464 publications

(218 citation statements)

References 4 publications

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“…3,6,44,45 Alveolar soft part sarcoma and renal cell carcinoma can further overlap in morphology with nested and alveolar growth patterns bounded by prominent sinusoidal vasculature with polygonal cells containing clear to eosinophilic cytoplasm and distinct borders. 25,[50][51][52] In addition, gene expression studies suggest Xp11.2 renal cell carcinoma is more closely related to alveolar soft part sarcoma than to typical clear cell renal cell carcinoma. 53 These studies suggest that Xp11.2 renal cell carcinoma may require a different treatment strategy without adjuvant chemotherapy compared with TFE3-negative renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

et al. 2014

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Renal cell carcinoma with TFE3 rearrangement at Xp11.2 is a distinct subtype manifesting an indolent clinical course in children, with recent reports suggesting a more aggressive entity in adults. This subtype is morphologically heterogeneous and can be misclassified as clear cell or papillary renal cell carcinoma. TFE3 is also rearranged in alveolar soft part sarcoma. To aid in diagnosis, a break-apart strategy fluorescence in situ hybridization (FISH) probe set specific for TFE3 rearrangement and a reflex dual-color, single-fusion strategy probe set involving the most common TFE3 partner gene, ASPSCR1, were validated on formalin-fixed, paraffinembedded tissues from nine alveolar soft part sarcoma, two suspected Xp11.2 renal cell carcinoma, and nine tumors in the differential diagnosis. The impact of tissue cut artifact was reduced through inclusion of a chromosome X centromere control probe. Analysis of the UOK-109 renal carcinoma cell line confirmed the break-apart TFE3 probe set can distinguish the subtle TFE3/NONO fusion-associated inversion of chromosome X. Subsequent extensive clinical experience was gained through analysis of 75 cases with an indication of Xp11.2 renal cell carcinoma (n ¼ 54), alveolar soft part sarcoma (n ¼ 13), perivascular epithelioid cell neoplasms (n ¼ 2), chordoma (n ¼ 1), or unspecified (n ¼ 5). We observed balanced and unbalanced chromosome X;17 translocations in both Xp11.2 renal cell carcinoma and alveolar soft part sarcoma, supporting a preference but not a necessity for the translocation to be balanced in the carcinoma and unbalanced in the sarcoma. We further demonstrate the unbalanced separation is atypical, with TFE3/ASPSCR1 fusion and loss of the derivative X chromosome but also an unanticipated normal X chromosome gain in both males and females. Other diverse sex chromosome copy number combinations were observed. Our TFE3 FISH assay is a useful adjunct to morphologic analysis of such challenging cases and will be applicable to assess the growing spectrum of TFE3-rearranged tumors.

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Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

et al. 2014

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“…Since the recognition of ASPS as a distinct clinicopathologic entity in 1952 (Christopherson et al, 1952), its cell of origin and biology have remained unclear. Its typical presentation is as an intra-or perimuscular thigh mass in a young woman, an observation con®rmed in the present group of patients (Table 1), but it has also been reported in tissues where skeletal muscle is absent, such as stomach, retroperitoneum, breast, and female genital tract, among others.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior. Recent cytogenetic studies have identi®ed a recurrent der(17) due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To de®ne the interval containing the Xp11.2 break, we ®rst performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region. This localized the breakpoint to a 160 kb interval. The prime candidate within this previously fully sequenced region was TFE3, a transcription factor gene known to be fused to translocation partners on 1 and X in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic probe identi®ed non-germline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. Ampli®cation of the 5' portion of cDNAs containing the 3' portion of TFE3 in two di erent ASPS cases identi®ed a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4 (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3 fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the utility of this assay in the diagnosis of ASPS. Using appropriate primers, the reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases, consistent with the non-reciprocal nature of the translocation in most cases, and supporting ASPL-TFE3 as its oncogenically signi®cant fusion product. ASPL maps to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a predicted protein of 476 amino acids that contains within its carboxy-terminal portion of a UBXlike domain that shows signi®cant similarity to predicted proteins of unknown function in several model organisms. The ASPL-TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of this tumor, consistent with the biology of several other translocationassociated sarcomas. Oncogene (2001) 20, 48 ± 57.

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“…Moreover, cathepsin K expression has not been evaluated in alveolar soft part sarcoma, a rare soft tissue sarcoma that harbors the same ASPSCR1-TFE3 gene fusion as a subset of Xp11 translocation renal cell carcinomas. [11][12][13] The purpose of this study was to evaluate the expression of cathepsin K in a series of wellcharacterized tumors harboring TFE3 gene fusions, including alveolar soft part sarcoma and genetically confirmed subtypes of Xp11 translocation renal cell carcinomas.…”

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confidence: 99%

Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions

et al. 2011

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Cathepsin K is a protease whose expression is driven by microphthalmia transcription factor (MITF) in osteoclasts. TFE3 and TFEB are members of the same transcription factor subfamily as MITF and all three have overlapping transcriptional targets. We have shown that all t(6;11) renal cell carcinomas, which harbor an Alpha-TFEB gene fusion, as well as a subset of the Xp11 translocation renal carcinomas, which harbor various TFE3 gene fusions, express cathepsin K, while no other common renal carcinoma does. We have hypothesized that overexpression of TFEB or certain TFE3 fusion proteins function like MITF in these neoplasms, and thus activate cathepsin K expression. However, the expression of cathepsin K in specific genetic subtypes of Xp11 translocation carcinomas, as well as alveolar soft part sarcoma, which harbors the same ASPSCR1-TFE3 gene fusion as some Xp11 translocation carcinomas, has not been addressed. We performed immunohistochemistry for cathepsin K on 14 genetically confirmed t(X;1)(p11;q21) carcinomas, harboring the PRCC-TFE3 gene fusion; eight genetically confirmed t(X;17)(p11;q25) carcinomas, harboring the ASPSCR1-TFE3 gene fusion; and 18 alveolar soft part sarcomas (12 genetically confirmed), harboring the identical ASPSCR1-TFE3 gene fusion. All 18 alveolar soft part sarcomas expressed cathepsin K. In contrast, all eight ASPSCR1-TFE3 carcinomas were completely negative for cathepsin K. However, 12 of 14 PRCC-TFE3 carcinomas expressed cathepsin K. Expression of cathepsin K distinguishes alveolar soft part sarcoma from the ASPSCR1-TFE3 carcinoma, harboring the same gene fusion. The latter can be useful diagnostically, especially when alveolar soft part sarcoma presents in an unusual site (such as bone) or with clear cell morphology, which raises the differential diagnosis of metastatic ASPSCR1-TFE3 renal cell carcinoma. The difference in expression of cathepsin K between the PRCC-TFE3 and ASPSCR1-TFE3 carcinomas, together with the observed clinical differences between these subtypes of Xp11 translocation carcinomas, suggests the possibility of functional differences between these two related fusion proteins.

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Alveolar soft-part sarcomas.Structurally characteristic tumors of uncertain histogenesis

Cited by 464 publications

References 4 publications

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

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

Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions

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