Juxtaglomerular cell tumors (JGCTs) are rare tumors characterized by renin synthesis, hyperaldosteronism and hypertension. A curious immunohistochemical overlap between JGCT and gastrointestinal stromal tumor (GIST) including the expression of vimentin, CD34, CD117, alpha-smooth muscle actin was previously reported, prompting us to further investigate JGCT and its phenotypic and molecular genetic characteristics. Virtual karyotyping showed gain of chromosomes 3, 4, 10, 13, 17 and 18 in one JGCT, and fluorescence in situ hybridization (FISH) study confirmed this multiple gain pattern. Additionally, loss of chromosome 9 was observed in four of six cases analyzed with FISH. A whole genome expression analysis revealed 415 up-regulated (including renin, and CD117) and 325 down-regulated genes between the 2 cases. The study confirmed earlier reports on the gain of chromosomes 4 and 10, and provided further evidence of up-regulation of the genes located on these 2 chromosomes. For the first time our study indicated the importance of the loss of chromosome 9 and loss of expression of several tumor suppressor genes located on this chromosome as possible pathogenetic events important in development of JGCT.Copyright © 2013 Elsevier Inc. All rights reserved.

• MeSH
• beta-katenin MeSH
• cytoplazmatická granula MeSH
• dospělí MeSH
• imunohistochemie MeSH
• juxtaglomerulární aparát MeSH
• karyotypizace MeSH
• lidé MeSH
• mladý dospělý MeSH
• protoonkogenní proteiny c-kit MeSH
• renin MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Cellular hypoxia is a hallmark of cancer. Hypoxia-inducible factor-1alpha (HIF-1alpha) and von Hippel-Lindau protein (pVHL) are the key mediators of cellular response to hypoxia. Little is known about their role in germ cell tumors of the testis. We therefore examined their status in a cohort of germ cell tumors of the testis. Thirty-six primary germ cell tumors of the testis (11 seminomas, 24 mixed germ cell tumors, and 1 case of pure intratubular germ cell neoplasia) were included in the study. HIF-1alpha and pVHL expression were studied using immunohistochemical (IHC) methods in the tumor and adjacent benign tissue. Selected cases with a low pVHL expression were further tested for genetic alterations using polymerase chain reaction. HIF-1alpha protein expression was not detectable in adjacent atrophic seminiferous tubules. In contrast, HIF-1alpha was expressed in one third of the malignancies, but in a low percentage of cells (mean, 3%; range, 0% to 20%). No difference in HIF-1alpha expression was observed between seminomas and nonseminomas (P=0.71). pVHL was expressed in atrophic tubular epithelium and in the Leydig cells, whereas a substantial loss of pVHL expression was observed in germ cell tumors regardless of the histologic type (mean, 45.6%; range, 0% to 100%). No genetic alterations of the VHL gene were observed in the cases with low pVHL expression. No significant correlation between HIF-1alpha and pVHL expression was observed (P=0.16). Germ cell tumors of the testis, regardless of the histologic type, are characterized by consistently low HIF-1alpha protein overexpression and a partial loss of pVHL without underlying VHL gene alterations. Further studies are necessary to clarify the functional importance of such alterations in testicular germ cell tumors.

• MeSH
• dospělí MeSH
• exony MeSH
• exprese genu * MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa * genetika   metabolismus   MeSH
• germinální a embryonální nádory * MeSH
• hypoxie buňky genetika   MeSH
• imunohistochemie MeSH
• Leydigovy buňky metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• nádorové mikroprostředí MeSH
• nádorový supresorový protein VHL * genetika   metabolismus   MeSH
• polymerázová řetězová reakce MeSH
• semenotvorné kanálky metabolismus   patologie   MeSH
• seminom * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH