Chromophobe renal cell carcinoma (ChRCC) is typically composed of large leaf-like cells and smaller eosinophilic cells arranged in a solid-alveolar pattern. Eosinophilic, adenomatoid/pigmented, or neuroendocrine variants have also been described. We collected 10 cases of ChRCC with a distinct multicystic pattern out of 733 ChRCCs from our registry, and subsequently analyzed these by morphology, immunohistochemistry, and array comparative genomic hybridization. Of the 10 patients, 6 were males with an age range of 50-89 years (mean 68, median 69). Tumor size ranged between 1.2 and 20 cm (mean 5.32, median 3). Clinical follow-up was available for seven patients, ranging 1-19 years (mean 7.2, median 2.5). No aggressive behavior was documented. We observed two growth patterns, which were similar in all tumors: (1) variable-sized cysts, resembling multilocular cystic neoplasm of low malignant potential and (2) compressed cystic and tubular pattern with slit-like spaces. Raisinoid nuclei were consistently present while necrosis was absent in all cases. Half of the cases showed eosinophilic/oncocytic cytology, deposits of pigment (lipochrome) and microcalcifications. The other half was composed of pale or mixed cell populations. Immunostains for epithelial membrane antigen (EMA), CK7, OSCAR, CD117, parvalbumin, MIA, and Pax 8 were positive in all tumors while negative for vimentin, TFE3, CANH 9, HMB45, cathepsin K, and AMACR. Ki67 immunostain was positive in up to 1 % of neoplastic cells. Molecular genetic examination revealed multiple chromosomal losses in two fifths analyzable tumors, while three cases showed no chromosomal numerical aberrations. ChRCC are rarely arranged in a prominent multicystic pattern, which is probably an extreme form of the microcystic adenomatoid pigmented variant of ChRCC. The spectrum of tumors entering the differential diagnosis of ChRCC is quite different from that of conventional ChRCC. The immunophenotype of ChRCC is identical with that of conventional ChRCC. Chromosomal numerical aberration pattern was variable; no chromosomal numerical aberrations were found in three cases. All the cases in this series have shown an indolent and non-aggressive behavior.

• Klíčová slova
• ArrayCGH, Chromophobe renal cell carcinoma, Immunohistochemistry, Kidney, Multicystic,
• MeSH
• chromozomální aberace MeSH
• diferenciální diagnóza MeSH
• imunohistochemie metody   MeSH
• karcinom z renálních buněk diagnóza   genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mucin 1 genetika   metabolismus   MeSH
• nádorové biomarkery analýza   MeSH
• nádory ledvin diagnóza   genetika   patologie   MeSH
• oxyfilní adenom diagnóza   genetika   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srovnávací genomová hybridizace metody   MeSH
• Check Tag
• 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
• mucin 1 MeSH
• nádorové biomarkery MeSH

Generally, patients with renal cell carcinoma (RCC) are viewed as potential candidates for antiangiogenic targeted therapy. Tubulocystic RCC (TCRC) is a recently described entity which may behave aggressively, and the rationale for antiangiogenic therapy in this group of renal tumors has yet to be determined. Seven TCRCs and five non-tumor tissue samples from seven patients were subjected to relative expression analysis of mRNA levels of 16 genes involved in three angiogenic signal pathways: (1) VHL/HIF, (2) RTK/mitogen-activated protein kinase (MAPK), and (3) PI3K/Akt/mTOR. Two of them, pathways (2) and (3), are often targeted by antiangiogenic agents. We also determined the mutation and methylation status of the VHL gene. Finally, the levels of vascular endothelial growth factor A (VEGFA), HIF-1α, HIF-2α proteins, and phosphorylated mTOR protein were also determined. The comparison of tumor and control samples revealed no changes of mRNA levels of the following genes: VHL, HIF-1α, HIF-2α, PTEN, Akt2, Akt3, mTOR, VEGFA, KDR, HRas, C-Jun, EGFR, and FGF2. Significantly elevated mRNA level of TP53 was found, while the mRNA levels of FLT1 and C-FOS were reduced in tumor samples. No mutations or methylation in the VHL gene were found. Changes in levels of studied proteins VEGFA, HIF-1α, HIF-2α, and increased phosphorylation of mTOR protein were not found. Three studied angiogenic pathways (VHL/HIF, RTK/MAPK, and PI3K/Akt/mTOR) seem not to be upregulated in TCRC samples, so there appears to be no rationale for a general recommendation of antiangiogenic targeted therapeutic protocols for patients with these tumors.

• MeSH
• cílená molekulární terapie metody   MeSH
• dospělí MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   MeSH
• fosforylace MeSH
• inhibitory angiogeneze farmakologie   terapeutické užití   MeSH
• karcinom z renálních buněk krevní zásobení   farmakoterapie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorový supresorový protein VHL metabolismus   MeSH
• nádory ledvin krevní zásobení   farmakoterapie   metabolismus   MeSH
• patologická angiogeneze farmakoterapie   genetika   MeSH
• senioři MeSH
• signální transdukce účinky léků   genetika   MeSH
• TOR serin-threoninkinasy metabolismus   MeSH
• transkripční faktory bHLH metabolismus   MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endothelial PAS domain-containing protein 1 MeSH Prohlížeč
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• HIF1A protein, human MeSH Prohlížeč
• inhibitory angiogeneze MeSH
• MTOR protein, human MeSH Prohlížeč
• nádorový supresorový protein VHL MeSH
• TOR serin-threoninkinasy MeSH
• transkripční faktory bHLH MeSH
• vaskulární endoteliální růstový faktor A MeSH
• VEGFA protein, human MeSH Prohlížeč
• VHL protein, human MeSH Prohlížeč