Prognostic Value of Invasion, Markers of Proliferation, and Classification of Giant Pituitary Tumors, in a Georeferred Cohort in Brazil of 50 Patients, with a Long-Term Postoperative Follow-Up.

Although some pituitary adenomas may have an aggressive behavior, the vast majority are benign. There are still controversies about predictive factors regarding the biological behavior of these particular tumors. This study evaluated potential markers of invasion and proliferation compared to current classification patterns and epidemiogeographical parameters. The study included 50 patients, operated on for tumors greater than 30 mm, with a mean postoperative follow-up of 15.2 ± 4.8 years. Pituitary magnetic resonance was used to evaluate regrowth, invasion, and extension to adjacent tissue. Three tissue biomarkers were analyzed: p53, Ki-67, and c-erbB2. Tumors were classified according to a combination of histological and radiological features, ranging from noninvasive and nonproliferative (grade 1A) to invasive-proliferative (grade 2B). Tumors grades 2A and 2B represented 42% and 52%, respectively. Ki-67 (p = 0.23) and c-erbB2 (p = 0.71) had no significant relation to tumor progression status. P53 (p = 0.003), parasellar invasion (p = 0.03), and classification, grade 2B (p = 0.01), were associated with worse clinical outcome. Parasellar invasion prevails as strong predictive factor of tumor recurrence. Severe suprasellar extension should be considered as invasion parameter and could impact prognosis. No environmental factors or geographical cluster were associated with tumor behavior.

Endothelin-1 levels in plasma and cerebrospinal fluid of patients with cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Plasma and cerebrospinal fluid (CSF) concentrations of endothelin-1 (ET-1) were measured in patients with subarachnoid hemorrhage (SAH) after aneurysmal rupture and compared with levels of ET-1 in volunteers. We analyze the relationship between levels of ET-1 in both CSF and plasma with the risk of developing cerebral vasospasm (CVS). METHODS: Cerebrospinal fluid and blood samples were collected from 30 selected patients after SAH and from 10 healthy volunteers who were used as control. All samples were stored at -70 degrees C and the levels of ET-1 in CSF and blood were measured by using enzyme-linked immunosorbent assay and Western blot. All patients were submitted to angiography to confirm vasospasm. RESULTS: From the 30 patients admitted at different days of SAH, 18 (60%) developed clinical CVS and 10 (33%) presented angiographic CVS. The levels of ET-1 in the CSF were significantly higher (P = .0001) in patients (1.618 +/- 1.05 fmol/mL) than in controls (0.365 +/- 0.328 fmol/mL). There was statistical difference (P < .05) in CSF levels of ET-1 between each group of the Hunt-Hess scale and controls. The mean plasma concentration of ET-1 was similar (P > .05) in the control group (1.531 +/- 0.753 fmol/mL) and in patients with SAH (1.920 +/- 1.15 fmol/mL). CONCLUSIONS: These findings indicate that a significant rise in ET-1 levels in the CSF, but not in the plasma, occurs in patients who develop CVS after SAH. Our observation suggests that ET-1 might be involved in the pathogenesis of SAH-associated CVS.

[Non-functioning pituitary adenomas: clinical features and immunohistochemistry]. / Caracterização clínica e imunoistoquímica dos adenomas clinicamente não-funcionantes de hipófise.

UNLABELLED: Clinically non-functioning pituitary adenomas do not produce clinical signs of hormonal hypersecretion. Therefore, signs and symptoms will depend on the mass effect of these adenomas over the central nervous system. Their etiopathogeny is complex and their development is probably influenced by several factors, such as hypothalamic hormones (GHRH), growth factors (FGF), proliferation factors (PCNA, and KI-67), protein P53 and the proto-oncogene c-erb-B2. OBJECTIVE: 1) Determining the clinical features of a population of 117 patients treated for clinically non-functioning pituitary adenoma (age, sex, tumor size, number of surgical procedures, development of hormonal deficiency and hyperprolactinemia). 2) Identifying, after the patients had been clinically characterized, those with clinically non-functioning adenomas with positive immunohistochemistry for hypophyseal hormones (PRL, LH, FSH, GH, TSH and ACTH). 3) Determining if the immunohistochemistry of this population was positive for the cellular proliferation factor Ki-67, protein P53 and protein C-erb-B2 and establishing a correlation with tumor size and tumor invasiveness. This will help in the evaluation of the prognostic value of these proliferation factors. 4) Confronting the results of immunohistochemistry using a standard block with the results of immunohistochemistry using a tissue micro-array. METHOD: Study of the clinical features of 117 patients with clinically non-functioning pituitary adenoma (age, sex, tumor size, number of surgical procedures, development of hormonal deficiency and hyperprolactinemia). Immunohistochemical study (H&E) of 39 patients for hypophyseal hormones, protein P53, protein C-erb-B2, Ki-67 to establish their correlation to tumor growth. The next step was a tissue micro-array of the 39 previously studied cases, using immunohistochemistry for hypophyseal hormones, protein P 53, protein C-erb-B2, Ki-67 to establish their correlation to tumor growth. RESULTS: There was no statistically significant difference between males and females with regards to age, tumor size and number of surgical procedures (p=0.279, p=813, p=139 respectively). There is a statistically significant correlation between the size of the tumor, the number of surgical procedures and hormonal deficiency (p=0.032, p=0.223 respectively). There was no statistically significant correlation between a positive immunohistochemistry for protein P53, protein C-erb-B2, Ki-67 and tumor size (r=0.182, p=0.396; r=-0.181, p=0.397; r=0.272, p=0.199, respectively). The tissue micro-array also did not demonstrate a correlation between positive immunohistochemistry for Ki-67 and C-erb-B2 and tumor size, but it showed a statistically significant correlation between a positive immunohistochemistry for p53 and tumor size (r=-0.696; p=001). CONCLUSION: The biological behavior of the clinically non-functioning adenoma is similar for both sexes. The larger the tumor the greater the number of surgical procedures needed. Hormonal deficiency also becomes more significant as the size of the tumor increases. This paper suggests that a positive immunohistochemistry for p53 is negatively correlated to tumor size, thus demonstrating that it has a predictor value. However, a positive immunohistochemistry for Ki-67 and protein C-erb-B2 does not seem to be a prognostic factor for clinically non-functioning pituitary adenomas, as is the case with other neoplasias.