Evaluation of Fumarate Hydratase and Hypoxia-Associated Proteins in HLRCC Syndrome and Sporadic Cutaneous Leiomyomas
Jyoti P Kapil, Nitin Chakravarti, Jonathan L Curry, Wei-Lien Wang, Victor G Prieto, Michael T Tetzlaff, Carlos Torres-Cabala. MD Anderson Cancer Center, Houston, TX
Background: Hereditary leiomyomatosis and renal cell carcinoma(HLRCC) is a rare autosomal dominant syndrome with predispositions for cutaneous and uterine leiomyomas and aggressive RCC. It is caused by a germ-line inactivating mutation in fumarate hydratase(FH) gene, thought to initiate a pseudohypoxic drive culminating in stabilization of hypoxia inducible factor-1a(HIF-1a). Little is known about the expression of the proteins involved in the postulated altered molecular pathway in HLRCC-related and sporadic cutaneous leiomyomas.
Design: 12 cutaneous leiomyomas and 1 smooth muscle tumor of uncertain malignant potential(SMTUMP) were examined for IHC expression of FH, HIF-1α, HIF-2α, and HIF-1α-associated downstream proteins lactate dehydrogenase-A(LDH-A) and glucose transporter-1(GLUT-1). Each marker was evaluated for intensity of expression(scale of 0 to 3), percentage of positive cells(0,1:<5%, 2:5-50%, 3:greater than 50%), and subcellular localization(nuclear, cytoplasmic, or both).
Results: The clinical and histologic features of the 13 cases:6 HLRCC pilar leiomyomas, 4 sporadic pilar leiomyomas, 2 angioleiomyomas and 1 SMTUMP were selected from patients(range 29-89 y/o) with a M:F ratio 4:5. Sites: arm(4), leg(4), shoulder(2), trunk(2), and foot(1). HLRCC patients also presented with metastatic renal carcinoma(1) and uterine leiomyomas(1).