Membrane-type metalloproteinases (including MMP-14 and MMP-15) are enzymes involved in the degradation of extracellular matrix components. In cancer, they are involved in processes such as cellular invasion, angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the expression, content and activity of MMP-14 and MMP-15 in human renal cell carcinoma. Samples of healthy kidney tissue (n = 20) and tissue from clear-cell kidney cancer (n = 20) were examined. The presence and contents of the MMPs were assessed using Western blot and ELISA techniques, respectively. Their activity-both actual and specific-was evaluated using fluorimetric analysis. Both control and cancer human kidney tissues contain MMP-14 and MMP-15 enzymes in the form of high-molecular-weight complexes. Moreover, these enzymes occur in both active and latent forms. Their content in cancer tissues is very similar, but with a noteworthy decrease in content with an increase in the kidney cancer grade for both membrane-type metalloproteinases. Even more notable is the highest content of the investigated enzymes represented by MMP-14 in the control tissues. Considering the actual and specific activity outcomes, MMP-14 dominates over MMP-15 in all of the investigated tissues. Nevertheless, we also noted a significant enhancement of the activity of both metalloproteinases with an increase in the grade of renal cancer. The expression and activity of both enzymes were detected in all examined renal cancer tissues. However, our findings suggest that transmembrane metalloproteinase 14 (MMP-14) plays a much more significant and essential role than MMP-15 in the studied renal carcinoma tissues. Therefore, it seems that MMP-14 could be a promising target in the diagnosis, prognosis and therapy of renal cell carcinoma.

• MeSH
• dospělí MeSH
• karcinom z renálních buněk * metabolismus   patologie   enzymologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 14 * metabolismus   MeSH
• matrixová metaloproteinasa 15 * metabolismus   genetika   MeSH
• nádory ledvin * patologie   metabolismus   enzymologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

ALK rearranged renal cell carcinoma (ALK-RCC) has recently been included in 2016 WHO classification as a provisional entity. In this study, we describe 12 ALK-RCCs from 8 institutions, with detailed clinical, pathological, immunohistochemical (IHC), fluorescence in situ hybridization (FISH), and next generation sequencing (NGS) analyses. Patients' age ranged from 25 to 68 years (mean, 46.3 years). Seven patients were females and five were males (M:F = 1:1.4). Tumor size ranged from 17 to 70 mm (mean 31.5, median 25 mm). The pTNM stage included: pT1a (n = 7), pT1b (n = 1), and pT3a (n = 4). Follow-up was available for 9/12 patients (range: 2 to 153 months; mean 37.6 months); 8 patients were alive without disease and one was alive with distant metastases. The tumors demonstrated heterogeneous, 'difficult to classify' morphology in 10/12 cases, typically showing diverse architectural and cellular morphologies, including papillary, tubular, tubulocystic, solid, sarcomatoid (spindle cell), rhabdoid, signet-ring cell, and intracytoplasmic vacuoles, often set in a mucinous background. Of the remaining two tumors, one showed morphology resembling mucinous tubular and spindle cell renal cell carcinoma (MTSC RCC-like) and one was indistinguishable from metanephric adenoma. One additional case also showed a focal metanephric adenoma-like area, in an otherwise heterogeneous tumor. By IHC, all tumors were diffusely positive for ALK and PAX8. In both cases with metanephric adenoma-like features, WT1 and ALK were coexpressed. ALK rearrangement was identified in 9/11 tumors by FISH. ALK fusion partners were identified by NGS in all 12 cases, including the previously reported: STRN (n = 3), TPM3 (n = 3), EML4 (n = 2), and PLEKHA7 (n = 1), and also three novel fusion partners: CLIP1 (n = 1), KIF5B (n = 1), and KIAA1217 (n = 1). ALK-RCC represents a genetically distinct entity showing a heterogeneous histomorphology, expanded herein to include unreported metanephric adenoma-like and MTSC RCC-like variants. We advocate a routine ALK IHC screening for "unclassifiable RCCs" with heterogeneous features.

• MeSH
• anaplastická lymfomová kináza genetika   MeSH
• dospělí MeSH
• fúze genů * MeSH
• genová přestavba * MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk enzymologie   genetika   sekundární   MeSH
• kineziny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádorové proteiny genetika   MeSH
• nádory ledvin enzymologie   genetika   patologie   MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• proteiny genetika   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Severní Amerika MeSH

Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.

• MeSH
• biopsie MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• dospělí MeSH
• dřeň ledvin enzymologie   patologie   MeSH
• fenotyp MeSH
• fumarasa nedostatek   genetika   MeSH
• genetická predispozice k nemoci MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk klasifikace   enzymologie   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery nedostatek   genetika   MeSH
• nádory ledvin klasifikace   enzymologie   genetika   patologie   MeSH
• prediktivní hodnota testů MeSH
• retrospektivní studie MeSH
• sběrací ledvinové kanálky enzymologie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Austrálie MeSH
• Brazílie MeSH
• Evropa MeSH
• Kanada MeSH
• Spojené státy americké MeSH

An emerging group of high-grade renal cell carcinomas (RCCs), particularly carcinomas arising in the hereditary leiomyomatosis renal cell carcinoma syndrome (HLRCC), show fumarate hydratase (FH) gene mutation and loss of function. On the basis of similar cytomorphology and clinicopathologic features between these tumors and cases described as tubulocystic carcinomas with poorly differentiated foci (TC-PD) of infiltrative adenocarcinoma, we hypothesized a relationship between these entities. First, 29 RCCs with morphology of TC-PD were identified retrospectively and assessed for FH expression and aberrant succination (2SC) by immunohistochemistry (IHC), with targeted next-generation sequencing of 409 genes-including FH-performed on a subset. The 29 TC-PD RCCs included 21 males and 8 females, aged 16 to 86 years (median, 46), with tumors measuring 3 to 21 cm (median, 9) arising in the right (n=16) and left (n=13) kidneys. Family history or stigmata of HLRCC were identifiable only retrospectively in 3 (12%). These tumors were aggressive, with 79% showing perinephric extension, nodal involvement in 41%, and metastasis in 86%. Of these, 16 (55%) demonstrated loss of FH by IHC (14/14 with positive 2SC). In contrast, 5 (17%) showed a wild-type immunoprofile of FH+/2SC-. An intriguing group of 8 (28%) showed variable FH± positivity, but with strong/diffuse 2SC+. Next-generation sequencing revealed 8 cases with FH mutations, including 5 FH-/2SC+ and 3 FH±/2SC+ cases, but none in FH+/2SC- cases. Secondly, we retrospectively reviewed the morphology of 2 well-characterized cohorts of RCCs with FH-deficiency determined by IHC or sequencing (n=23 and n=9), unselected for TC-PD pattern, identifying the TC-PD morphology in 10 (31%). We conclude that RCCs with TC-PD morphology are enriched for FH deficiency, and we recommend additional workup, including referral to genetic counseling, for prospective cases. In addition, based on these and other observations, we propose the term "FH-deficient RCC" as a provisional term for tumors with a combination of suggestive morphology and immunophenotype but where genetic confirmation is unavailable upon diagnosis. This term will serve as a provisional nomenclature that will enable triage of individual cases for genetic counseling and testing, while designating these cases for prospective studies of their relationship to HLRCC.

• MeSH
• dědičné nádorové syndromy patologie   MeSH
• dospělí MeSH
• fumarasa nedostatek   genetika   MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk enzymologie   genetika   patologie   MeSH
• leiomyomatóza patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• multiplexová polymerázová řetězová reakce MeSH
• nádory dělohy patologie   MeSH
• nádory kůže patologie   MeSH
• nádory ledvin enzymologie   genetika   patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• analýza přežití MeSH
• cílená molekulární terapie metody   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• karcinom z renálních buněk * enzymologie   farmakoterapie   patologie   MeSH
• lidé MeSH
• metastázy nádorů farmakoterapie   MeSH
• nádory ledvin farmakoterapie   patologie   MeSH
• nežádoucí účinky léčiv MeSH
• pyrimidiny terapeutické užití   MeSH
• retrospektivní studie MeSH
• sulfonamidy terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH

• MeSH
• hypertenze farmakoterapie   chemicky indukované   MeSH
• inhibitory angiogeneze aplikace a dávkování   škodlivé účinky   MeSH
• karcinom z renálních buněk * diagnóza   enzymologie   farmakoterapie   MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• prognóza MeSH
• protinádorové látky aplikace a dávkování   škodlivé účinky   MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor antagonisté a inhibitory   škodlivé účinky   MeSH
• syndrom ruka-noha epidemiologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH

Succinate dehydrogenase (SDH)-deficient renal carcinoma has been accepted as a provisional entity in the 2013 International Society of Urological Pathology Vancouver Classification. To further define its morphologic and clinical features, we studied a multi-institutional cohort of 36 SDH-deficient renal carcinomas from 27 patients, including 21 previously unreported cases. We estimate that 0.05% to 0.2% of all renal carcinomas are SDH deficient. Mean patient age at presentation was 37 years (range, 14 to 76 y), with a slight male predominance (M:F=1.7:1). Bilateral tumors were observed in 26% of patients. Thirty-four (94%) tumors demonstrated the previously reported morphology at least focally, which included: solid or focally cystic growth, uniform cytology with eosinophilic flocculent cytoplasm, intracytoplasmic vacuolations and inclusions, and round to oval low-grade nuclei. All 17 patients who underwent genetic testing for mutation in the SDH subunits demonstrated germline mutations (16 in SDHB and 1 in SDHC). Nine of 27 (33%) patients developed metastatic disease, 2 of them after prolonged follow-up (5.5 and 30 y). Seven of 10 patients (70%) with high-grade nuclei metastasized as did all 4 patients with coagulative necrosis. Two of 17 (12%) patients with low-grade nuclei metastasized, and both had unbiopsied contralateral tumors, which may have been the origin of the metastatic disease. In conclusion, SDH-deficient renal carcinoma is a rare and unique type of renal carcinoma, exhibiting stereotypical morphologic features in the great majority of cases and showing a strong relationship with SDH germline mutation. Although this tumor may undergo dedifferentiation and metastasize, sometimes after a prolonged delay, metastatic disease is rare in the absence of high-grade nuclear atypia or coagulative necrosis.

• MeSH
• čipová analýza tkání MeSH
• dospělí MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk enzymologie   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutační analýza DNA MeSH
• nádory ledvin enzymologie   genetika   patologie   MeSH
• polymerázová řetězová reakce MeSH
• senioři MeSH
• sukcinátdehydrogenasa biosyntéza   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• analýza podle původního léčebného záměru MeSH
• analýza přežití * MeSH
• časové faktory MeSH
• fenylmočovinové sloučeniny škodlivé účinky   terapeutické užití   MeSH
• imidazoly škodlivé účinky   terapeutické užití   MeSH
• indazoly škodlivé účinky   terapeutické užití   MeSH
• inhibitory proteinkinas * škodlivé účinky   terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z renálních buněk * enzymologie   farmakoterapie   mortalita   MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• nádory ledvin enzymologie   farmakoterapie   mortalita   MeSH
• niacinamid analogy a deriváty   škodlivé účinky   terapeutické užití   MeSH
• přežití bez známek nemoci MeSH
• proporcionální rizikové modely MeSH
• protinádorové látky * škodlivé účinky   terapeutické užití   MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• sorafenib MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

• MeSH
• antigeny nádorové krev   moč   MeSH
• finanční podpora výzkumu jako téma MeSH
• karboanhydrasy krev   moč   MeSH
• karcinom z renálních buněk enzymologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery krev   moč   MeSH
• nádorové proteiny krev   moč   MeSH
• nádory ledvin enzymologie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH