Renal Cell Carcinomas With t(6;11)(p21;q12)

Rao, Qiu; Liu, Biao; Liu, Cheng; Zhu, Yun; Shi, Qun li; Wu, Bo; Jiang, Shengwei; Wang, Yan; Wang, Xuan; Yu, Bo; Zhang, Ru song; Hui, Heng; Lu, Zhen; Tu, Pin; Wang, Jian Dong; Zhou, Xiao

doi:10.1097/pas.0b013e31825aafb5

Cited by 72 publications

(24 citation statements)

References 34 publications

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“…Despite the epithelioid morphology that suggested carcinoma, these neoplasms did not label for epithelial immunohistochemical markers but instead demonstrated focal labeling for melanocytic markers HMB45 and melan-A, which raised the question of whether these neoplasms represented RCC or variants of epithelioid angiomyolipoma. With greater clinical experience and broader immunohistochemical analysis, it has become clearer that these neoplasms represent RCCs which clinically, morphologically, and immunohistochemically overlap with the Xp11 translocation RCC 2,3,4,5,6 . Though both may occur in adults, both the Xp11 translocation RCC and the t(6;11) RCC disproportionately affect young patients.…”

Section: Introductionmentioning

confidence: 99%

TFEB-amplified Renal Cell Carcinomas

Argani

Reuter

Zhang

et al. 2016

American Journal of Surgical Pathology

109

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Renal cell carcinomas (RCCs) with the t(6;11)(p21;q12) chromosome translocation are low grade RCC which often occur in young patients. They typically feature an unusual biphasic morphology characterized by nests of larger epithelioid cells surrounding intraluminal collections of smaller cells clustered around basement membrane material. The t(6;11)(p21;q12) translocation fuses the Alpha (MALAT1) gene with the TFEB transcription factor gene, resulting in upregulated expression of intact native TFEB that drives the aberrant expression of melanocytic markers which is a hallmark of this distinctive neoplasm. We now report 8 cases of RCC which demonstrate TFEB gene amplification (6 without TFEB rearrangement, 2 with concurrent TFEB rearrangement) and demonstrate downstream consequences of TFEB overexpression. Like the unamplified t(6;11) RCC, all TFEB-amplified RCC were associated with aberrant melanocytic marker expression. However, several differences between TFEB-amplified RCC and the usual unamplified t(6;11) RCC are evident. First, TFEB-amplified RCC occurred in older patients (median age 64.5 years) compared with unamplified t(6;11) RCC (median age 31 years). Second, the morphology of TFEB-amplified RCC is not entirely distinctive, frequently featuring nests of high grade epithelioid cells with eosinophilic cytoplasm associated with pseudopapillary formation and necrosis, or true papillary formations. These patterns raise the differential diagnosis of high grade clear cell and papillary RCC. Third, TFEB and melanocytic marker expression was more variable within the TFEB-amplified RCC. TFEB protein expression by immunohistochemistry was detectable in 6 of 8 cases. While all 8 cases expressed melan-A, only 5 of 8 expressed cathepsin K and only 3 of 8 expressed HMB45. Fourth, the TFEB-amplified RCC were associated with a more aggressive clinical course; 3 of 8 cases presented with advanced stage or metastatic disease, 2 subsequently developed metastatic disease, while the other 3 cases had minimal/no follow-up. Our results are corroborated by scant data reported on 6 TFEB-amplified RCC in the literature, gleaned from 1 case report, 1 abstract, and 4 individual cases identified within two genomic studies of large cohorts of RCC. In summary, TFEB-amplified RCC represent a distinct molecular subtype of high grade adult RCC associated with aggressive clinical behavior, variable morphology, and aberrant melanocytic marker expression.

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Section: Introductionmentioning

confidence: 99%

TFEB-amplified Renal Cell Carcinomas

Argani

Reuter

Zhang

et al. 2016

American Journal of Surgical Pathology

109

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“…1,6–10 In addition, the t(6;11) RCCs label for cathepsin K, a protease that is expressed in osteoclasts but that is not present in non–MiT family translocation RCCs. 7,11,12 …”

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confidence: 99%

“…The studies are generally characterized by small sample sizes and a limited number of IHC markers. 6,7 Moreover, therapeutic targets have not been identified. In this study, we provide a more complete IHC characterization of t(6;11) RCC with a diverse range of markers.…”

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confidence: 99%

t(6;11) Renal Cell Carcinoma (RCC)

Smith¹,

Illei²,

Allaf³

et al. 2014

American Journal of Surgical Pathology

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Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Uro-logical Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cath-epsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that metastasize.

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“…Citations of articles used in the table: Argani et al 2007 Rais-Bahrami et al 2007 LaGrange et al 2007 Franzini et al 2007 Hora et al 2008 Camparo et al 2008 Hora et al 2009 Suarez-Vilela et al 2011, Koie et al 2009 Armah et al 2009 Kuroda et al 2010 Choueiri et al 2010 Ishihara et al 2011 Liu et al 2011 Nelius et al 2011 Numakura et al 2011, Kato et al 2011 Klatte et al 2012 Morii et al 2012 Rao et al 2012 Inamura et al 2012 Arnoux et al 2012 Komai et al 2009 Gaillot-Durand et al 2013.…”

Section: Resultsmentioning

confidence: 99%

“…This tumour harbours translocations involving the transcription factor EB (TFEB) and Alpha (the latter also known as MALATI ). Genetically, TFEB RCC has been characterized by the fusion of the 5’ portion of Alpha , also known as MALATI (Genbank accession number AF203815), an intronless gene mapped at 11q12, with TFEB at 6p21 Inamura et al 2012; Rao et al 2012 with fewer than 30 cases reported to date Hora et al 2009; Inamura et al 2012; Rao et al 2012; Camparo et al 2008; Suarez-Vilela et al 2011. First 11 cases were reviewed by Hora et al 2009, cases published since 2007 are summarised in Table 1.…”

Section: Discussionmentioning

confidence: 99%

MiT translocation renal cell carcinomas: two subgroups of tumours with translocations involving 6p21 [t (6; 11)] and Xp11.2 [t (X;1 or X or 17)]

et al. 2014

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IntroductionMiT translocation renal cell carcinomas (TRCC) predominantly occur in younger patients with only 25% of patients being over 40 years. TRCC contains two main subgroups with translocations involving 6p21 or Xp11.2. Herein we present 10 cases.MaterialsEight cases were treated at main author’s institution (identified among 1653 (0.48%) cases of kidney tumours in adults). Two cases were retrieved from the Pilsen (CZ) Tumour Registry.ResultsSix cases were type Xp11.2 and four 6p21; 7 female, 3 male patients; Xp11.2 4:2, 6p21 3:1. The mean age 49 years (range: 21–80), 5 patients (50%) over 40 years. The mean age of the group with Xp11.2 TRCCs was 55 (median 51) and 6p21 41 (32) years. One female with a 6p21 tumour (24 years) underwent nephrectomy at 4 months of pregnancy. Stage (UICC, 7th ed. 2009) was 5xI, 3xIII, 2xIV. The mean size of tumour was 80 (40–165) mm. The mean follow-up was 33.2 (1–92) months. In patients with 6p21 tumours, one (25%) died after 3 months due to widely metastatic disease. In patients with Xp11.2 tumours, 3 (50%) succumbed due to metastatic disease (range 1–8 months). Three patients with Xp11.2 are alive at 7, 52 and 92 months of follow-up, were diagnosed at early stage (T1a).ConclusionTRCCs were more common in females. Patient with 6p21 tumours were younger than those with Xp11.2. Both types have definitive malignant potential Type Xp11.2 seems to be a more aggressive neoplasm than 6p21. The case with metastatic 6p21 tumour is the 4th case described in the English literature.

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Renal Cell Carcinomas With t(6;11)(p21;q12)

Cited by 72 publications

References 34 publications

TFEB-amplified Renal Cell Carcinomas

TFEB-amplified Renal Cell Carcinomas

t(6;11) Renal Cell Carcinoma (RCC)

MiT translocation renal cell carcinomas: two subgroups of tumours with translocations involving 6p21 [t (6; 11)] and Xp11.2 [t (X;1 or X or 17)]

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