RESUMEN
BACKGROUND: Osteoprotegerin (OPG), receptor activator of nuclear factor kappaB (RANK), RANK ligand (RANKL), and TNF related apoptosis inducing ligand (TRAIL) are the key proteins in the development of bone metastases. Osteoprotegerin improves tumor cell survival and inhibits TRAIL induced apoptosis of cancer cell lines. It also binds to RANKL and inhibits its interaction with RANK (cell surface receptor), which influences osteoclast formation and function. The aim of the present study was to characterize the expression of OPG, RANK, RANKL, and TRAIL in benign and malignant thyroid tissue and thyroid cell lines. METHODS: Archived thyroid tissue from 79 patients (60 differentiated thyroid cancers and 19 benign thyroids) was stained for OPG, RANK, RANKL, and TRAIL by immunohistochemistry. Staining was assessed semiquantitatively and correlated with pathology. Western blots were performed on three human thyroid cell lines: Nthy-ori 3-1 (thyroid follicular epithelium), FTC-133 (follicular thyroid carcinoma), and K1E7 (subclone of papillary thyroid carcinoma). RESULTS: Osteoprotegerin and RANKL staining was cytoplasmic; RANK staining was nuclear; and TRAIL staining was predominantly cytoplasmic. All four proteins were expressed in benign and malignant tissue. There was significant difference in RANK expression between malignant and benign tissue (8 vs. 84%, respectively; Fisher's exact test; P < 0.001). RANKL expression was significantly increased in malignant tissue (Fisher's exact test; P = 0.04). Western blotting showed OPG expression in all cell lines and TRAIL in none. RANK and RANKL were not detected in papillary and follicular cell lines, respectively. CONCLUSIONS: Nuclear expression of RANK protein in thyroid tissue is paradoxical; it could be due to nuclear migration after ligand binding. Suppression of RANK and increased expression of RANKL in malignant tissue warrant further investigation.
Asunto(s)
Biomarcadores de Tumor/análisis , Osteoprotegerina/análisis , Ligando RANK/análisis , Ligando Inductor de Apoptosis Relacionado con TNF/análisis , Enfermedades de la Tiroides/genética , Neoplasias de la Tiroides/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biopsia con Aguja , Western Blotting , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Osteoprotegerina/genética , Ligando RANK/genética , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Enfermedades de la Tiroides/metabolismo , Enfermedades de la Tiroides/patología , Enfermedades de la Tiroides/cirugía , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Adulto JovenRESUMEN
Solitary rectal ulcer syndrome is a rare condition that is associated with disordered defecation and is thought to be an ischemic injury from repeated mucosal trauma. Treatment is designed to alleviate the underlying defecatory problems and is only moderately successful. We report an interesting case of solitary rectal ulcer syndrome in a young woman, which was resistant to standard nonoperative management but completely resolved during two pregnancies only to recur when she was not pregnant, and we suggest a possible hormonal explanation for this unique occurrence.
