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)

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• 作者：Petr Martínek ; Petr Grossmann ; Ond?ej Hes ; Ji?í Bouda ; Viktor Eret…
• 关键词：HLRCC ; Fumarate hydratase ; FH Leiomyoma ; Renal cell carcinoma
• 刊名：Virchows Archiv
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：467
• 期：2
• 页码：185-191
• 全文大小：542 KB
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  2.Sanz-Ortega J, Vocke C, Stratton P, Linehan WM, Merino MJ (2013) Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome. Am J Surg Pathol 37(1):74-0. doi:10.-097/?PAS.-b013e31825ec16f-/span> PubMed Central PubMed View Article
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  4.Reyes C, Karamurzin Y, Frizzell N, Garg K, Nonaka D, Chen Y, Soslow R (2014) Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry. Mod Pathol 27(7):1020-027PubMed Central PubMed View Article
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  8.Bardella C, El-Bahrawy M, Frizzell N et al (2011) Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status. J Pathol 225:4-1PubMed View Article
  9.Ewbank C, Kerrigan JF, Aleck K (2006) Fumarate Hydratase Deficiency http://?www.?ncbi.?nlm.?nih.?gov/?books/?NBK1506/-/span> . Accesed 24 May 2014
  10.Deschauer M, Gizatullina Z, Schulze A, Pritsch M, Kn?ppel C, Knape M, Zierz S, Gellerich FN (2006) Molecular and biochemical investigations in fumarase deficiency. Mol Genet Metab 88(2):146-52PubMed View Article
  11.Wong MH, Tan CS, Lee SC, Yong Y, Ooi AS, Ngeow J, Tan MH (2014) Potential genetic anticipation in hereditary leiomyomatosis renal cell cancer (HLRCC). Fam Cancer 13:281-89. doi:10.-007/?s10689-014-9703-x PubMed View Article
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• 作者单位：Petr Martínek (1) (2)
  Petr Grossmann (2)
  Ond?ej Hes (1)
  Ji?í Bouda (3)
  Viktor Eret (4)
  Norma Frizzell (5)
  Anthony J Gill (6) (7)
  Ondrej Ondi? (1) (2)
  
  1. ?ikl’s Department of Pathology, University Hospital, Faculty of Medicine in Pilsen, Charles University in Prague, alej Svobody 80, 304 60, Pilsen, Czech Republic
  2. Department of Genetics, Bioptická laborato? s.r.o, Pilsen, Czech Republic
  3. Department of Gynecology and Obstetrics, University Hospital, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic
  4. Department of Urology, University Hospital, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic
  5. Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, Columbia, SC, USA
  6. Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia
  7. University of Sydney, Sydney, NSW, Australia
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Pathology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-2307

文摘

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.