Translocation Carcinomas of the Kidney After Chemotherapy in Childhood

Argani, Pedram; Laé, Marick; Ballard, Edgar T.; Amin, Mahul B.; Manivel, Carlos; Hutchinson, Brian; Reuter, Victor E.; Ladanyi, Marc

doi:10.1200/jco.2005.04.4693

Cited by 224 publications

(146 citation statements)

References 24 publications

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“…All the cases had been earlier reported and cytogenetically confirmed. 2,3,5,[12][13][14][15][16][17] Seven cases harbored the translocation t(6;11)(p21;q12), which results in an Alpha-TFEB gene fusion and all showed confirmatory TFEB nuclear immunoreactivity as described earlier. 5 Ten cases had translocations involving Xp11.2, and all ten of these renal cell carcinomas showed confirmatory TFE3 nuclear immunoreactivity as described earlier.…”

Section: Tissue Samplessupporting

confidence: 66%

Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas

Pea²,

et al. 2009

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The microphthalmia transcription factor/transcription factor E (TFE)-family translocation renal cell carcinomas bear specific translocations that result in overexpression of TFE3 or TFEB. TFE3 fusion gene product overexpression occurs as consequence of different translocations involving chromosome Xp11.2, whereas TFEB overexpression is the result of the specific translocation t(6;11)(p21;q12), which fuses the Alpha gene to TFEB. Both TFE3 and TFEB are closely related members of the microphthalmia transcription factor/TFE-family, which also includes TFEC and microphthalmia transcription factor. These transcription factors have overlapping transcriptional targets. Overexpression of microphthalmia transcription factor has been shown to mediate the expression of cathepsin-K in osteoclasts. We hypothesize that the overexpression of the related TFE3 fusion proteins and TFEB in translocation renal cell carcinomas may have the same effect. We studied cathepsin-K in 17 cytogenetically confirmed microphthalmia transcription factor/TFE-family translocation renal cell carcinomas. Seven cases showed a t(6;11)(p21;q12), ten cases showed translocations involving Xp11.2; five cases t(X;1)(p11;q21) resulting in a PRCC-TFE3 gene fusion; three cases t(X;1)(p11;p34) resulting in a PSF-TFE3 gene fusion, one t(X;17)(p11;q25) resulting in an ASPL-TFE3 gene fusion, and one t(X;3)(p11;q23) with an unknown TFE3 gene fusion. As control we analyzed cathepsin-K in 210 clear cell, 40 papillary, 25 chromophobe renal cell carcinomas and 30 oncocytomas. All seven TFEB translocation renal cell carcinomas were labeled for cathepsin-K. Among the cytogenetically confirmed TFE3 translocation renal cell carcinomas, 6 out of 10 were positive. None of the other renal neoplasms expressed cathepsin-K. We conclude the following: (1) cathepsin-K is consistently and strongly expressed in TFEB translocation renal cell carcinomas and in 6 of 10 TFE3 translocation renal cell carcinomas. (2) Cathepsin-K immunolabeling in both TFE3 and TFEB translocation renal cell carcinomas distinguishes these neoplasms from the more common adult renal cell carcinomas, and may be a specific marker of these neoplasms. (3) These results further support the concept that the overexpression of TFE3 or TFEB in these neoplasms activates the expression of genes normally regulated by microphthalmia transcription factor in other cell types. Keywords: cathepsin-K; TFE3; TFEB; translocation; renal cell carcinoma; immunohistochemistryThe recently described microphthalmia transcription factor/transcription factor E (MiTF/TFE) family translocation renal cell carcinomas comprise the majority of pediatric renal cell carcinomas but also occur in adults. MiTF/TFE family translocation renal cell carcinomas are characterized by specific chromosome aberrations involving the genes transcription factor E3 (TFE3) and transcription factor EB (TFEB). The TFE3 transcription factor gene maps to chromosomal region Xp11.2, whereas the TFEB transcription factor gene maps to chromosome 6p21. 1,2 Several disti...

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Section: Tissue Samplessupporting

confidence: 66%

Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas

Pea²,

et al. 2009

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“…As this tumor generally occurs in children and young adults, urologists and pathologists should take the differential diagnosis of renal tumor arising in children and young adults into consideration [6,7,8,9,10,11,12,13]. As observed in the present study, this tumor may occur even at the age over 40 years [14,15,16,17,18,19,20].…”

Section: Discussionsupporting

confidence: 50%

“…As observed in the present study, this tumor may occur even at the age over 40 years [14,15,16,17,18,19,20]. In some cases, previous cytotoxic chemotherapy may be involved in the pathogenesis of this tumor [8]. Therefore, the presence of a past history is very important for urologists.…”

Section: Discussionmentioning

confidence: 53%

Clinicopathological study of 5 cases of renal cell carcinoma with t(6;11)(p21;q12)

Yorita

Sasaki

Ishihara

et al. 2017

pjp

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Renal cell carcinoma (RCC) with t(6;11)(p21;q12) has been incorporated into the recent WHO classification. We performed a clinicopathological study of 5 cases with such a tumor. The patients consisted of 4 males and 1 female. The age of patients ranged from 17 to 57 years with a mean age of 38.6 years. Tumor sizes ranged from 2.8 to 11 cm with a mean value of 6.5 cm. Despite immunotherapy and molecular-targeted therapy, one patient died of the disease 28 months after the surgery. Grossly, the cut surface of this tumor showed grayish white color in at least the focal area of all tumors. Furthermore, hemorrhage, daughter nodules and cystic changes were observed in two, three, and two tumors, respectively. Morphologically, all the tumors consisted of two components of large cells and small cells, and the latter surrounded basement membrane-like materials, forming rosette-like structures. Immunohistochemically, nuclei of tumor cells in all cases were positive for TFEB. Fluorescence in situ hybridization study confirmed the TFEB gene break in two tumors. Finally, urologists and pathologists should bear in mind that this tumor may occur in young adults to adults and might behave in an aggressive fashion. Break-apart FISH is useful for the definite diagnosis.

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“…6,8,14,15 We also identified 14 cases of genetically confirmed t(X;1)(p11;q21) translocation renal cell carcinomas, which harbor the PRCC-TFE3 gene fusion, of which 13 have previously been reported. 14,16,17 All of these displayed a strong nuclear immunoreactivity for TFE3 (Figure 2f and h). Finally, we identified 18 cases of alveolar soft part sarcoma, which consistently (100% of cases tested in the literature) harbor the ASPSCR1-TFE3 gene fusion.…”

Section: Tissue Samplesmentioning

confidence: 95%

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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Translocation Carcinomas of the Kidney After Chemotherapy in Childhood

Abstract: Cytotoxic chemotherapy may predispose to the development of renal translocation carcinomas.

Cited by 224 publications

References 24 publications

Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas

Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas

Clinicopathological study of 5 cases of renal cell carcinoma with t(6;11)(p21;q12)

Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions

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