Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome secondary to germline fumarate hydratase (FH) mutation presents with cutaneous and uterine leiomyomas, and a distinctive aggressive renal carcinoma. Identification of HLRCC patients presenting first with uterine leiomyomas may allow early intervention for renal carcinoma. We reviewed the morphology and immunohistochemical (IHC) findings in patients with uterine leiomyomas and confirmed or presumed HLRCC. IHC was also performed on a tissue microarray of unselected uterine leiomyomas and leiomyosarcomas. FH-deficient leiomyomas underwent Sanger and massively parallel sequencing on formalin-fixed paraffin-embedded tissue. All 5 patients with HLRCC had at least 1 FH-deficient leiomyoma: defined as completely negative FH staining with positive internal controls. One percent (12/1152) of unselected uterine leiomyomas but 0 of 88 leiomyosarcomas were FH deficient. FH-deficient leiomyoma patients were younger (42.7 vs. 48.8 y, P=0.024) and commonly demonstrated a distinctive hemangiopericytomatous vasculature. Other features reported to be associated with FH-deficient leiomyomas (hypercellularity, nuclear atypia, inclusion-like nucleoli, stromal edema) were inconstantly present. Somatic FH mutations were identified in 6 of 10 informative unselected FH-deficient leiomyomas. None of these mutations were found in the germline. We conclude that, while the great majority of patients with HLRCC will have FH-deficient leiomyomas, 1% of all uterine leiomyomas are FH deficient usually due to somatic inactivation. Although IHC screening for FH may have a role in confirming patients at high risk for hereditary disease before genetic testing, prospective identification of FH-deficient leiomyomas is of limited clinical benefit in screening unselected patients because of the relatively high incidence of somatic mutations.
- MeSH
- čipová analýza tkání MeSH
- dospělí MeSH
- fenotyp MeSH
- fumarasa nedostatek genetika MeSH
- genetická predispozice k nemoci MeSH
- imunohistochemie MeSH
- leiomyomatóza enzymologie genetika patologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nádorové biomarkery nedostatek genetika MeSH
- nádory dělohy enzymologie genetika patologie chirurgie MeSH
- nádory kůže enzymologie genetika patologie chirurgie MeSH
- prognóza MeSH
- syndrom MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Fumarate hydratase (FH) is a key enzyme of the Krebs cycle. Germline mutations in the FH gene encoding fumarate hydratase cause autosomal dominant syndromes multiple cutaneous and uterine leiomyomata and hereditary leiomyomatosis and renal cell cancer (HLRCC). Few data have been published on the role of FH gene mutation in development of uterine fibroids outside the context of multiple cutaneous and uterine leiomyomata /HLRCC. We report two FH gene mutations, one novel and one previously described, in two young patients with sporadic uterine fibroids and decreased fumarate hydratase activity in lymphocytes. In patient 1, a novel heterozygous mutation c.892G>C was found. In patient 2 we detected heterozygous mutation c.584T>C. Both the patients had a negative family history for renal cancer and cutaneous leiomyomatosis. None of the relatives, however, underwent renal imaging at the time of writing. FH mutation carriers may be easily identified by analysis of fumarate hydratase activity in blood lymphocytes. We suggest performing fumarate hydratase activity or FH mutation screening in women with onset of uterine fibroids in their 20s and family history of uterine fibroids or other HLRCC-associated malignancies.
- MeSH
- dospělí MeSH
- fumarasa genetika MeSH
- leiomyom enzymologie genetika chirurgie ultrasonografie MeSH
- lidé MeSH
- mutace MeSH
- myomektomie MeSH
- nádory dělohy enzymologie genetika chirurgie ultrasonografie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
To determine clinical benefits of mRNA aromatase expression in entopic endometrium as a diagnostic marker of endometriosis. DESIGN: Prospective clinical trial. SETTING: Department of Obstetrics and Gynaecology of Jessenius Medical Faculty and Faculty Hospital, Martin. METHODS: The expression of mRNA aromatase of eutopic endometrium was determined among women who underwent laparoscopy or laparotomy due to pelvic pain, infertility or benign pelvic tumor. Endometriosis was confirmed histologicaly and classified by rAFS. RESULTS: On the basis of entering criteria 23 women were enrolled in this study and divided into two subgroups: 12 endometriotic and 11 without endometriosis. Sensitivity of aromatase expression was 75% and specificity 54.5% at the cut-off value of at least minimal aromatase activity. By the presence of estrogen-dependent diseases- endometriosis, myomas or endometrial hyperplasia 18 women were compared to 5 disease free women. In this case, sensitivity of aromatase expression was 72.2 and specificity 80%. CONCLUSION: Aromatase expression in eutopic endometrium is a good diagnostic marker for endometriosis.
- MeSH
- aromatasa genetika metabolismus MeSH
- biologické markery analýza MeSH
- dospělí MeSH
- endometrióza diagnóza enzymologie MeSH
- endometrium enzymologie MeSH
- estrogeny fyziologie MeSH
- hyperplazie endometria diagnóza enzymologie MeSH
- leiomyom diagnóza enzymologie MeSH
- lidé MeSH
- messenger RNA analýza MeSH
- nádory dělohy diagnóza enzymologie MeSH
- polymerázová řetězová reakce MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- MeSH
- alanintransaminasa krev MeSH
- alkalická fosfatasa krev MeSH
- aspartátaminotransferasy krev MeSH
- chuť MeSH
- cytochrom B2 krev MeSH
- hyperplazie endometria enzymologie patofyziologie MeSH
- lidé MeSH
- nádory dělohy enzymologie patofyziologie MeSH
- thiokarbamáty MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
