Genetic testing of leiomyoma tissue in women younger than 30 years old might provide an effective screening approach for the hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC)
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
- MeSH
- dědičné nádorové syndromy MeSH
- dospělí MeSH
- fumarasa genetika MeSH
- genetická predispozice k nemoci MeSH
- genetické testování metody MeSH
- imunohistochemie MeSH
- leiomyom genetika MeSH
- leiomyomatóza diagnóza genetika MeSH
- lidé MeSH
- mladý dospělý MeSH
- mutační analýza DNA MeSH
- nádory dělohy diagnóza genetika MeSH
- nádory kůže diagnóza genetika MeSH
- pilotní projekty MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- senzitivita a specificita MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fumarasa MeSH
We have studied the viability of targeted molecular screening for the identification of female patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. Affected patients harbor a germ-line heterozygous mutation of the fumarate hydratase (FH) gene. Clinically, some patients present with aggressive renal cell carcinoma. Concerning women, in almost all cases, this is preceded by symptomatic uterine leiomyoma. We aimed to identify women operated on for symptomatic leiomyoma by the age of 30. Archived paraffin-embedded leiomyoma tissue was tested for the FH gene mutation in 14 cases. Two patients with multiple leiomyomas and with the confirmed germ-line mutations c.1433_1434dupAAA, p.(Lys477dup) and c.953A>T, p.(His318Leu) were identified and enrolled in a surveillance program. Statistically significant correlation between the presence of multiple uterine leiomyomas (more than seven in our experience) and the FH gene mutation was found. The immunohistochemical expression pattern, of simultaneous FH absence and S-(2-succino)cysteine (2SC) positivity, correlated with the results of the molecular genetic study in only one case. The histomorphologically simultaneous detection of enlarged nucleoli with a clear halo of leiomyocyte nuclei, their fibrillary cytoplasm, the presence of eosinophilic globules, and staghorn vessels proved to be only a partially sensitive indicator of HLRCC-associated leiomyoma and fully correlated with immunohistochemistry and molecular genetic study only in one case. Molecular genetic testing is presently the only reliable diagnostic tool able to identify HLRCC patients. The sensitivity and specificity of the presence of multiple leiomyomas in women with the FH gene mutation who are younger than 30 years old should be confirmed in larger scale studies. The applied targeted molecular screening protocol proved to be effective, resulting in identification of two positive patients out of fourteen tested individuals.
Zobrazit více v PubMed
Mol Genet Metab. 2006 Jun;88(2):146-52 PubMed
Mod Pathol. 2014 Jul;27(7):1020-7 PubMed
Fam Cancer. 2014 Jun;13(2):281-9 PubMed
Am J Surg Pathol. 2013 Oct;37(10):1469-89 PubMed
J Biol Chem. 2007 Nov 23;282(47):34219-28 PubMed
J Pathol. 2011 Sep;225(1):4-11 PubMed
Am J Surg Pathol. 2013 Jan;37(1):74-80 PubMed
J Cutan Pathol. 2014 Nov;41(11):859-65 PubMed
Am J Hum Genet. 2003 Jul;73(1):95-106 PubMed
Am J Surg Pathol. 2014 May;38(5):627-37 PubMed
Leukemia. 2003 Dec;17(12):2257-317 PubMed
Cancer Res. 2002 Aug 15;62(16):4554-7 PubMed
Hum Mutat. 2011 May;32(5):557-63 PubMed
Fumarate Hydratase-deficient Uterine Leiomyomas Occur in Both the Syndromic and Sporadic Settings
