Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.

Male gonadal function, prolactin secretion and lactotroph population in an experimental model of cirrhosis

Liver cirrhosis, a highly prevalent chronic disease, is frequently associated with endocrine dysfunctions, notably in the gonadal axis. We evaluated lactotroph population by immunohistochemistry, gonadotropins and prolactin by immunoradiometric assay and testosterone and estradiol by radioimmunoassay in adult male Wistar rats with cirrhosis induced by carbon tetrachloride. No significant difference in mean ± SEM percentages of lactotrophs was found between cirrhotic animals and controls (N = 12, mean 18.95 ± 1.29 percent). Although there was no significant difference between groups in mean serum levels of prolactin (control: 19.2 ± 4 ng/mL), luteinizing hormone (control: 1.58 ± 0.43 ng/mL), follicle-stimulating hormone (control: 19.11 ± 2.28 ng/mL), estradiol (control: 14.65 ± 3.22 pg/mL), and total testosterone (control: 138.41 ± 20.07 ng/dL), 5 of the cirrhotic animals presented a hormonal profile consistent with hypogonadism, all of them pointing to a central origin of this dysfunction. Four of these animals presented high levels of estradiol and/or prolactin, with a significant correlation between these two hormones in both groups (r = 0.54; P = 0.013). It was possible to detect the presence of central hypogonadism in this model of cirrhotic animals. The hyperestrogenemia and hyperprolactinemia found in some hypogonadal animals suggest a role in the genesis of hypogonadism, and in the present study they were not associated with lactotroph hyperplasia.

Expression of p53 protein in pituitary adenomas

Inactivating mutations of TP53, a tumor suppressor gene, are associated with abnormal cell proliferation. Although p53 expression is common in many human malignancies, p53 protein has seldom been evaluated in pituitary tumors. When detected, the percentage of p53-positive cells is low, and, in general, it is exclusive for invasive lesions. The aim of the present study was to use immunohistochemistry to determine the presence of p53 protein in pituitary adenomas from tumor samples of 163 surgeries performed in 148 patients (40 percent male, 60 percent female). In 35 percent of the cases the adenoma was nonfunctional, while in the others it was associated with PRL, GH and/or ACTH endocrine hypersecretion syndrome. Macroadenomas were observed in 83.2 percent of the cases with available neuroimage evaluation, of which 28 percent invaded the cavernous, sphenoid and/or ethmoidal sinus, bone, third ventricle or subfrontal lobe. p53 protein was detected in 2/148 patients (1.3 percent). Immunohistochemistry was positive for PRL and GH in these cases. Due to the high percentage of invasive pituitary adenomas found in our study, the low frequency of p53 detection suggests that it is inadequate as a routine marker for aggressiveness and as a predictive factor of tumor behavior

Aversive stimulation during the stress-hyporesponsive period does not affect the number of corticotroph cells in neonatal male rats

Immunohistochemistry was used to evaluate the effects of neonatal handling and aversive stimulation during the first 10 days of life on the number of corticotrophs in the anterior lobe of the pituitary of 11-day-old male Wistar rats. Since adult rats handled during infancy respond with reduced corticosterone secretion in response to stressors and with less behavior inhibition in novel environments, we assumed that neonatal stimulation could affect pituitary morphology during this critical period of cell differentiation. Three groups of animals were studied: intact (no manipulation, N=5), handled (N=5) and stimulated (submitted to 3 different aversive stimuli, N=5). The percentage of ACTH-immunoreactive cells in the anterior lobe of the pituitary (number of ACTH-stained cells divided by total number of cells) was determined by examining three slices per pituitary in which a minimum of 200 cells were counted by two independent researchers. Although animals during the neonatal period are less reactive to stress-like stimulation in terms of ACTH and corticosterone secretion, results showed that the relative number of ACTH-stained cells of neonatal handled (0.25 + 0.01) and aversive stimulated (0.29 + 0.03) rats was not significantly different from intact (0.30 + 0.03) animals. Neonatal stimulation may have a differential effect on the various subpopulations of corticotroph cells in the anterior pituitary.

Effects of bromocriptine on serum prolactin levels, pituitary weight and immunoreactive prolactin cells in estradiol-treated ovariectomized rats: an experimental model of estrogen-dependent hyperprolactinemia

The present study was designed to assess the effects of bromocriptine, a dopamine agonist, on pituitary wet weight, number of immunoreactive prolactin cells and serum prolactin concentrations in estradioltreated rats. Ovariectomized Wistar rats were injected subcutaneously with sunflower oil vehicle or estradiol valerate (50 or 300 mug rat-1 week-l) for 2, 4 or 10 weeks. Bromocriptine (0.2 or 0.6 mg rat-1 day-l) was injected daily during the last 5 or 12 days of estrogen treatment. Data were compared with those obtained for intact control rats. Administration of both doses of estrogen increased serum prolactin levels. No difference in the number of prolactin cells in rats treated with 50 mug estradiol valerate was observed compared to intact adult animals. In contrast, rats treated with 300 mug estradiol valerate showed a significant increase in the number of prolactin cells (P<0.05). Therefore, the increase in serum prolactin levels observed in rats treated with 50 mug estradiol valerate, in the absence of morphological changes in the pituitary cells, suggests a "functional" estrogen-induced hyperprolactinemia. Bromocriptine decreased prolactin levels in all estrogen-treated rats. The administration of this drug to rats previously treated with 300 mug estradiol valerate also resulted in a significant decrease in pituitary weight and number of prolactin cells when compared to the group treated with estradiol alone. The general antiprolactinemic and antiproliferative pituitary effects of bromocriptine treatment reported here validate the experimental model of estrogen-induced hyperprolactinemic rats.

Effect of estrogen and neuroleptics on prolactin secretion and immunoreactive prolactin cells

The use of estrogen and dopamine receptor antagonists is associated with elevated prolactin levels and, in rats, chronic estrogen treatment is also associated with lactotroph proliferation. In this study, haloperidol, fluphenazine, sulpiride and metoclopramide, alone or combined with estradiol, were administered to Wistar rats. Pituitary weight, serum prolactin levels and percent of immunoreactive prolactin cells in the anterior pituitary glands were determined at the end of 60 days of treatment. The pituitary weight of rats treated with estrogen alone or in combination with other drugs was significantly higher than the control group. The serum prolactin level was higher than the upper confidence limit in all but three of the 90 treated rats. While in the control group the percent of immunoreactive prolactin cells was 20 per cent, administration of the neuroleptic drugs and metoclopramide increased this percent to approximately 30 per cent, and estrogen alone or in combination with one of the neuroleptic drugs increased it to approximately 40 per cent. The results presented here demonstrate the elationship between prolactin secretion and prolactin cell number when different neuroleptics and related drugs are used.

Effects of norethisterone acetate and tamoxifen on serum prolactin levels, uterine growth and on the presence of uterine immunoreactive prolactin in estradiol-treated ovariectomized rats

The aim of the present work was to study the effects of the antiestrogen tamoxifen 9TAM) of progestin noresthisterone acetite (NA) and of their combination on serum prolactin levels, uterine growth and the presence of uterine immunoreactive prolactin estradiol- treated rats. Ovariectomized female Wistar rats were injected sc with estradiol valerate (VE, 50 µg/rat per week) or oil vehicle. During the secon week, estradiol-treated rats also received NA (0.12 or 1.0 mg/eat, sc, daily) or TAM (0.06 mg/rat) alone or in combination with NA (0.12mg). Serum prolactin levels were suppressed to the same extent in the TAM- and 1.0 mg NA-treated groups compared with rats given estrogen alone (2.3 ñ 0.3 and 5.6 ñ 1.5 ng/ml for TAM and NA groups vs 39.7 ñ 3.6 ng/ml for VE groups, P < 0.05). Except for the lowes dose of NA, uterine wet weight and DNA content were significant reduced in all groups compared to estradiol alone (236.8 ñ 18.0 and 295.6 ñ 27.8 mg vs 309.4 ñ 32.2 mg for uterine weight in TAM and NA groups vs VE, respectively, P 0.05; and 1.14 ñ 0.05 and 0.93 ñ 0.04 mg/uterus vs 1.33 ñ 0.06 mg/uterus for uterine DNA in TAM and NA groups vs VE groups). The combination of NA and TAM resulted in a higher degree of suppression of uterine growth than when each drug was used alone, indicating an additive antiproliferative effect of NA and TAM. Although no prolactin immunostaining was detected in the uterus of rats treated with estradiol, uterine immunoreactive prolactin was identified in those treated with NA, TAM ot both. These results suggest that an inhibitory effect on the action of estradiol can play a role in the hormonal modulation of uterine secretion

Histoplasmomas encefalicos multiplos: estudo autopsico de um caso. / Multiple brain histoplasmomas: study of an autopsy of a case

E relatado um caso de paciente feminina, 28 anos, preta, que iniciou sintomatologia por disturbios de comportamento e, alguns meses apos apresentou alteracoes neurologicas. A tomografia computadorizada do encefalo revelou lesoes granulomatosas multiplas, com calcificacao. A paciente faleceu e a autopsia revelou lesoes encefalicas granulomatosas, com necrose central do tipo caseosa, que demonstrou, ao exame microscopico, serem produzidas pelo Histoplasma capsulatum. Os autores ressaltam ser o primeiro caso de histoplasma encefalico publicado no Brasil. Assinalam tambem a importancia da tomografia computadorizada no diagnostico das lesoes, bem como as alteracoes do liquido cefalorraquidiano encontradas nesses casos

Sarcoma de Kaposi gastrico. / Gastric Kaposi's sarcoma

Um caso de sarcoma de Kaposi, com envolvimento do estomago e apresentado.Ocasionalmente o trato gastrointestinal e comprometido. Sao comentados os aspectos clinicos, radiologicos e patologicos do Sarcoma de Kaposi