Loss of Fumarate Hydratase and Aberrant Protein Succination Detected With S-(2-Succino)-Cysteine Staining to Identify Patients With Multiple Cutaneous and Uterine Leiomyomatosis and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.
OBJECTIVE
Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance, and clinically challenging to diagnose. Immunohistochemical stainings may favor an earlier diagnosis.


RESULTS
The authors have tested 31 smooth muscle neoplasms. Ten of the 13 lesions from patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented strongly positive FH staining although 5 cases were negative. Sensitivity of FH staining in our series is 83.3% but specificity is 75%. Anti-S-(2-succino)-cysteine (2SC) showed the opposite intensity staining pattern and showed great correlation with anti-FH (rho spearman = -0.797). Anti-2SC staining increased the diagnostic accuracy in 19% of the cases.


CONCLUSIONS
The main limitation of this study is the lack additional clinical data to further classify the cases as the case inclusion was histopathological.


CONCLUSIONS
Negative FH staining could indicate a high risk of HLRCC but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. Thus, when there is a doubtful case, anti-2SC may be added to exclude the syndrome if a negative staining is found.
*Department of Dermatology, Hospital De La Princesa, Madrid, Spain; †Department of Dermatology, Fundación Jimenez Diaz, Madrid, Spain; ‡Department of Pathology, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, United Kingdom; §Department of Pharmacology, Physiology and Neurosciences, School of Public Health, University of South Carolina, Columbia, SC; ¶Institute of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany; and ‖Dermatopathologie Friedrichshafen, Friedrichshafen, Germany.
Mar
M
Llamas-Velasco
Luis
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Requena
Julie
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Adam
Norma
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Frizzell
Arndt
A
Hartmann
Thomas
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Mentzel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D003545:Cysteine / Q000031:analogs & derivatives* / Q000032:analysis; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D055088:Early Detection of Cancer; D005260:Female; D005649:Fumarate Hydratase / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D018231:Leiomyomatosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009386:Neoplastic Syndromes, Hereditary; D011237:Predictive Value of Tests; D011499:Protein Processing, Post-Translational; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
D014408:Biomarkers, Tumor; C511650:S-(2-succinyl)cysteine; D005649:Fumarate Hydratase; D003545:Cysteine