TFEB is overexpressed in TFEB-rearranged renal cell carcinomas as well as in renal tumors with amplifications of TFEB at 6p21.1. As recent literature suggests that renal tumors with 6p21.1 amplification behave more aggressively than those with rearrangements of TFEB, we compared relative TFEB gene expression in these tumors. This study included 37 TFEB-altered tumors: 15 6p21.1-amplified and 22 TFEB-rearranged (including 5 cases from The Cancer Genome Atlas data set). TFEB status was verified using a combination of fluorescent in situ hybridization (n=27) or comprehensive molecular profiling (n=13) and digital droplet polymerase chain reaction was used to quantify TFEB mRNA expression in 6p21.1-amplified (n=9) and TFEB-rearranged renal tumors (n=19). These results were correlated with TFEB immunohistochemistry. TFEB-altered tumors had higher TFEB expression when normalized to B2M (mean: 168.9%, n=28), compared with non-TFEB-altered controls (mean: 7%, n=18, P=0.005). Interestingly, TFEB expression in tumors with rearrangements (mean: 224.7%, n=19) was higher compared with 6p21.1-amplified tumors (mean: 51.2%, n=9; P=0.06). Of note, classic biphasic morphology was only seen in TFEB-rearranged tumors and when present correlated with 6.8-fold higher TFEB expression (P=0.00004). Our results suggest that 6p21.1 amplified renal tumors show increased TFEB gene expression but not as much as t(6;11) renal tumors. These findings correlate with the less consistent/diffuse expression of downstream markers of TFEB activation (cathepsin K, melan A, HMB45) seen in the amplified neoplasms. This suggests that the aggressive biological behavior of 6p21.1 amplified renal tumors might be secondary to other genes at the 6p21.1 locus that are co-amplified, such as VEGFA and CCND3, or other genetic alterations.

• MeSH
• dítě MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk diagnóza   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory ledvin diagnóza   metabolismus   patologie   MeSH
• následné studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory BHLH-Zip metabolismus   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nádorové biomarkery MeSH
• TFEB protein, human MeSH Prohlížeč
• transkripční faktory BHLH-Zip MeSH

Renal cell carcinomas with t(6;11) chromosome translocation involving the TFEB gene are indolent neoplasms which often occur in young patients. In this study, we report seven cases of renal cell carcinoma with TFEB rearrangement, two of whom had histologically proven metastasis. Patients (4F, 3M) ranged in age from 19 to 55 years (mean 37). One patient developed paratracheal and pleural metastases 24 months after surgery and died of disease after 46 months; another one recurred with neoplastic nodules in the perinephric fat and pelvic soft tissue. Histologically, either cytological or architectural appearance was peculiar in each case whereas one tumor displayed the typical biphasic morphology. By immunohistochemistry, all tumors labelled for cathepsin K, Melan-A and CD68 (KP1 clone). HMB45 and PAX8 staining were detected in six of seven tumors. All tumors were negative for CD68 (PG-M1 clone), CKAE1-AE3, CK7, CAIX, and AMACR. Seven pure epithelioid PEComa/epithelioid angiomyolipomas, used as control, were positive for cathepsin K, melanocytic markers, and CD68 (PG-M1 and KP1) and negative for PAX8. Fluorescence in situ hybridization results showed the presence of TFEB gene translocation in all t(6;11) renal cell carcinomas with a high frequency of split TFEB fluorescent signals (mean 74%). In the primary and metastatic samples of the two aggressive tumors, increased gene copy number was observed (3-5 fluorescent signals per neoplastic nuclei) with a concomitant increased number of CEP6. Review of the literature revealed older age and larger tumor size as correlating with aggressive behavior in these neoplasms. In conclusion, we present the clinical, morphological and molecular features of seven t(6;11) renal cell carcinomas, two with histologically demonstrated metastasis. We report the high frequency of split signals by FISH in tumors with t(6;11) chromosomal rearrangement and the occurrence of TFEB gene copy number gains in the aggressive cases, analyzing either the primary or metastatic tumor. Finally, we demonstrate the usefulness of CD68 (PG-M1) immunohistochemical staining in distinguishing t(6;11) renal cell carcinoma from pure epithelioid PEComa/epithelioid angiomyolipoma.

• MeSH
• angiomyolipom chemie   patologie   MeSH
• antigeny diferenciační myelomonocytární analýza   MeSH
• CD antigeny analýza   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk chemie   genetika   sekundární   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• lidské chromozomy, pár 6 genetika   MeSH
• nádorové biomarkery analýza   MeSH
• nádory ledvin chemie   genetika   patologie   MeSH
• nádory z perivaskulárních epiteloidních buněk chemie   patologie   MeSH
• transkripční faktory BHLH-Zip genetika   MeSH
• translokace genetická MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD68 antigen, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• TFEB protein, human MeSH Prohlížeč
• transkripční faktory BHLH-Zip MeSH