Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: A high throughput tma, immunohistochemical study
Por:
Ramírez C., Cheng S., Vargas G., Asa S.L., Ezzat S., González B., Cabrera L., Guinto G., Mercado M.
Publicada:
1 may 2012
Resumen:
Context: Nonfunctioning pituitary adenomas (NFPA) are the most common pituitary neoplasms. There is no clinical, biochemical, or histopathological marker that would accurately predict recurrence of NFPA. Objective: The aim of this study was to evaluate a large group of NFPA for the presence of potential markers of biological behavior. Design and Setting: Across-sectional study using a high throughput tissue microarray technology was conducted at tertiary care centers. Materials and Methods: Seventy-four gonadotroph and null cell adenomas were included in the tissue microarray. Using highly specific antibodies and appropriate controls, we determined the expression of Ki-67, pituitary tumor transforming gene 1, the N-terminally truncated pituitary tumor-derived fibroblast growth factor receptor-4(FGFR4), as well as somatostatin receptor subtypes 2, 3, and 5 (SSTR2, -3, and -5), in an attempt to establish correlations and/or associations with clinical characteristics of the patients. Results: Median Ki-67 indexwas 1.49 (interquartile range, 0.62-2.49). Pituitary tumor transforming gene 1 nuclear immunoreactivity was found in all but one tumor (median percentage of positive nuclei, 11.44); immunopositivity for FGFR4 was found in the majority of the tumors, with variable levels of expression. The immunostaining score for SSTR2 was significantly higher than that for SSTR3 or SSTR5. FGFR4 expression correlated positively with SSTR2 and SSTR5 immunostaining scores (r = 0.59; P < 0.001; and r = 0.46; P < 0.001, respectively). Multivariate analysis revealed that the Ki-67 index was significantly associated with a tumor size greater than 3 cm (odds ratio, 2.32; 95% confidence interval, 1.17-4.58) as well as with tumor recurrence (odds ratio, 1.4; 95% confidence interval, 1.03-1.89). Conclusions: Ki-67 is the most consistent marker of biological behavior in NFPA. The finding of significant amounts of SSTR2 and SSTR5 may have therapeutic implications regarding the use of somatostatin analogs in preventing tumor recurrence. Copyright © 2012 by The Endocrine Society.
Filiaciones:
Ramírez C.:
Endocrinology Service, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Aristóteles 68, Polanco, 11560 México City, Mexico
Cheng S.:
Department of Pathology, University Health Network, Ontario Cancer Center, Toronto, ON M5G 2C4, Canada
Department of Medicine, University Health Network, Ontario Cancer Center, Toronto, ON M5G 2C4, Canada
Vargas G.:
Endocrinology Service, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Aristóteles 68, Polanco, 11560 México City, Mexico
Asa S.L.:
Department of Pathology, University Health Network, Ontario Cancer Center, Toronto, ON M5G 2C4, Canada
Ezzat S.:
Department of Medicine, University Health Network, Ontario Cancer Center, Toronto, ON M5G 2C4, Canada
González B.:
Endocrinology Service, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Aristóteles 68, Polanco, 11560 México City, Mexico
Cabrera L.:
Department of Pathology, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, 11560 México City, Mexico
Guinto G.:
Department of Neurosurgery, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, 11560 México City, Mexico
Mercado M.:
Endocrinology Service, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Aristóteles 68, Polanco, 11560 México City, Mexico
Bronze
|