Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rare case of a stromal Leydig cell tumor of the ovary occurring in a 21-year-old woman who developed signs of virilization during pregnancy is reported. Serum androgen levels were markedly elevated. At cesarean section, a slightly hypotrophic, but otherwise normal, female infant was delivered and a tumor of the right ovary measuring 12 cm in maximum diameter was resected. Histologic examination revealed a sex cord-stromal tumor consisting of spindle-shaped, thecomatous cells and a large number of loosely scattered clusters of large polygonal cells with abundant eosinophilic cytoplasm. Both types of tumor cells were strongly immunoreactive for vimentin, but exhibited no proliferative activity and no overexpression of p53 protein. A few of the polygonal cells contained typical crystalloids of Reinke. Cellular atypia was not a prominent feature, and a diagnosis of benign stromal Leydig cell tumor was established. As expected, 20 months after diagnosis the patient exhibits no signs of recurrence or dissemination. To the best of our knowledge this is only the second case of a stromal Leydig cell tumor occurring in pregnancy to be described.
 ...
PMID:Virilizing stromal Leydig cell tumor (Leydig cell-containing thecoma) of the ovary in pregnancy. A case report with extensive immunohistochemical investigation of the tumor cells. 854 8

Prognostic markers in pediatric adrenal cortical tumors are difficult to define. We determined the ploidy, immunostaining of p53-protein and number of nucleolar organizer regions (AgNORs) in 16 such tumors and related them to clinical outcome, tumor weight (TW) and histologic Weiss' criteria. Eleven females and 5 males aged 0.4 to 15.6 years were followed for 8.7 years; 10 presented Cushing's and 6 virilization syndrome. Diploid (n = 4, x TW = 269 g, range: 17-800 g) and near-diploid tumors (n = 3, x TW = 55 g, range: 20-85 g) had good outcome, Weiss' criteria were 0-7, and p53 reactivity was negative in all. Among the aneuploid tumors (n = 9, x TW = 298 g, range: 7-1000 g), 6 had good outcome, 2 presented metastasis and 1 was lost to follow-up; Weiss' criteria were 2-8 and p53 reactivity was positive in 3 tumors (2 of them of malignant evolution). AgNORs number was not different in cases of good or poor outcome (3.65 +/- 1.9 vs 2.83 +/- 1.1). Our findings indicate that diploid and near-diploid cases had always a good outcome regardless of tumor weight. In aneuploid cases, tumor weights < 100 g had good outcome, while those > 750 g had poor prognosis. Malignant tumors were aneuploid and had reactivity to p53-protein. Good outcome in aneuploid tumors < 100 g is probably due to early treatment. The expression of p53-protein appears as a promising marker of poor prognosis. Weiss' criteria and AgNORs were not useful in the present series.
 ...
PMID:Functional adrenal cortical tumors in childhood: a study of ploidy, p53-protein and nucleolar organizer regions (AgNORs) as prognostic markers. 982 10

Adrenal cortical carcinoma (ACC) is a rare neoplasm that affects all age groups, with a bimodal peak of incidence, in young individuals in the first decade or two of life and in older subjects in the fifth to seventh decades. It may be clinically "functional" with Cushing's syndrome, virilization, or feminization, or it may be "nonfunctional." We report on the case of a 42-yr-old woman who complained of abdominal pain and a large adrenal tumor measuring 20 cm in size. No endocrine symptoms were observed. Laboratory tests showed increased levels of adrenocorticotropic hormone (ACTH), serum cortisol, and urinary free cortisol. Cytohistologic features were typical of ACC. A striking presence of hyaline cytoplasmatic globules was seen in cytologic smears and histologically, being immunoreactive for vimentin, consistent with an intracellular store of intermediate filaments. The tumor showed high proliferative activity (40%) with Ki-67 and negativity for p53, cerbB2, and bcl-2. Although hyaline globules are more frequent in pheochromocytomas and other neoplasms, they may also be present in ACC. These globules may be observed in cytologic smears. Also, the identification and immunohistochemical characterization of these hyaline globules in metastases may be useful in determining the origin of primary occult tumors. Diagn. Cytopathol. 1999;21:394-397.
 ...
PMID:Giant adrenal cortical carcinoma, clinically "nonfunctional": report of a case containing cytoplasmic hyaline globules of vimentin. 1057 70

It has been previously shown that adrenocortical tumors (ACT) in adults exhibit structural abnormalities in tumor DNA in approximately 30% of cases. These abnormalities involve chromosome 11p15 and include loss of heterozygosity, paternal isodisomy, and overexpression of the gene for insulin-like growth factor II (IGF2), correlating with DNA demethylation at this locus. It has been hypothesized that these events occur late in the tumorigenic process in adults and seem to correlate with a worse prognosis. We present 4 pediatric cases of ACT diagnosed at 2.5 yr, 10 months, 12 yr, and 2.2 yr. All 4 patients presented with virilization, and 1 patient also showed signs and symptoms of glucocorticoid excess. The youngest patient's maternal aunt had surgical excision of a more than 15-cm ACT 18 yr previously, but the aunt is doing well at age 23 yr. They all had surgical removal of their tumors. The 2.5-yr-old child also received chemotherapy and radiotherapy because of capsular rupture and, after 3 local recurrences, died 3.3 yr after initial presentation. We investigated all 4 tumors for chromosome 11 structural abnormalities (11p15.5 to 11q23), IGF2 and H19 expression by competitive RT-PCR analysis, and IGF2 methylation patterns by Southern analysis. All 4 tumors (100%) showed a combination of structural abnormalities at the 11p15 locus with mosaic loss of heterozygosity involving 11p. All tumors also had significantly increased IGF2 messenger ribonucleic acid levels relative to normal adrenal (up to 36-fold) and significant IGF2 demethylation (mean, 87%). H19 messenger ribonucleic acid levels were undetectable in 3 of 4 tumors, explained in part by mosaic loss of the actively expressed maternal allele for this imprinted gene. By immunohistochemistry we were able to confirm increased IGF-II peptide levels within the tumor tissue in 10 pediatric patients, including the 4 patients described above. Concomitantly, we also observed nuclear accumulation of p53, suggesting somatic mutations. For the 10-month-old patient, sequencing revealed a p53 germline mutation. We therefore conclude that in pediatric ACT, structural abnormalities of tumor DNA and IGF2 overexpression as well as p53 mutations are very common and are therefore less useful for prognosis than in adults. Our findings support the theory that pediatric ACT, whose IGF2 expression and steroidogenesis evoke the phenotype of the fetal adrenal cortex, may arise because of defective apoptosis.
 ...
PMID:Pediatric adrenocortical tumors: molecular events leading to insulin-like growth factor II gene overexpression. 1084 95

Childhood adrenocortical tumors (ACT) are very aggressive endocrine neoplasms whose incidence is quite low. Little is known about their pathogenesis, clinical presentation, and optimal treatment. In recent years, however, new information has been derived from the International Pediatric Adrenocortical Tumor Registry (IPACTR), and new clues to its pathogenesis have emerged. To provide an overview of the available data that may apply to pediatric ACT, we reviewed the epidemiology, pathogenesis, and treatment of ACT in adults and in children. Germline TP53 mutation is almost always the predisposing factor in childhood ACT. A unique germline mutation (TP53-R337H) has been described in Southern Brazil, where the incidence of ACT is 10-15 times the general incidence. Childhood ACT typically present during the first 5 years of life and has female predominance. Hormone hyperproduction is almost universal, and most patients present with virilization. Two-thirds of patients have resectable tumors. Surgery is the definitive treatment for ACT, and a curative complete resection should always be attempted. Cisplatin-based chemotherapy with mitotane is indicated for unresectable or metastatic disease, although its impact on overall outcome is slight. In childhood ACT, age, tumor size, and tumor resectability are the most important prognostic indicators. Outcome is stage-dependent; patients with small, resectable tumors have survival rates in excess of 80%, whereas the outcome for patients with unresectable disease is dismal. Patients with large, resectable tumors have an intermediate outcome. Childhood ACT are rare, but their unique epidemiology appear to implicate novel oncogenic pathways that are unique to the pediatric population. Multi-institutional and prospective studies are necessary to further our understanding of the pathogenesis and to improve outcomes.
 ...
PMID:Biology, clinical characteristics, and management of adrenocortical tumors in children. 1574 38

Adrenocortical tumors (ACTs) are frequent in Brazil. The mechanisms of adrenal tumorigenesis remain poorly established; the R337H germline mutation in the p53 gene has previously been associated with ACTs in Brazilian children. We investigated the frequency and inheritance of R337H p53 mutation as well as genotype and phenotype correlation in 21 children and 5 adult patients with ACTs. DNA was extracted from peripheral blood cells and/or tumor tissue for sequencing exon 10 of the p53 gene. Nine sets of parents of patients with p53 mutation were also submitted to mutational analysis. Virilization was the most common clinical sign in children with or without Cushing's syndrome. Two members of the adult group showed asymptomatic adrenal incidentalomas, two showed virilization, and one presented with Cushing's syndrome. Sixteen children with ACTs had peripheral blood available, and twelve of them (75%) showed the heterozygous R337H p53 gene mutation. The R337H mutation was found in fifteen samples of the nineteen tumor specimens available (78.9%). Among the nine sets of parents of the patients with R337H mutation, eight showed the same mutation with heterozygosity in one of the parents. None of the parents showed ACTs or any other neoplasia at the time of the study. Only one adult patient with an ACT revealed the same R337H p53 germline mutation. There was no association between the presence of germline or tissue R337H p53 mutation and malignancy at diagnosis. We confirmed the high frequency of R337H p53 mutation in Brazilian children with sporadic ACTs. The R337H p53 mutation was inherited from one of the parents of the patients, and there was no association between the presence of this mutation and tumor malignancy in children. The founder effect of R337H p53 mutation and the role of environmental mutagens contributing to the geographical clustering and high prevalence of ACTs in Brazilian children remain to be established.
 ...
PMID:Inheritance of R337H p53 gene mutation in children with sporadic adrenocortical tumor. 1595 83

Adrenocortical tumors are rare in children and are associated with a poor prognosis when malignant. The fund of knowledge regarding etiology, presentation and clinical outcomes remains limited. Evaluation of genetic disorders associated with the development of adrenocortical disorders has allowed researchers to identify a number of mutations that may be involved in tumorigenesis, including alterations in the GNAS1, PRKAR1A, TP53 and IGF2 genes. Clinical presentation in children is associated most commonly with young age, female gender and symptoms of virilization. Most children have localized disease at presentation which may be associated with a better prognosis when compared to adults. Surgical resection remains the only potentially curative treatment and mitotane, the most frequently used chemotherapeutic agent, has a poor response rate and is highly toxic. Broader participation in multi-center research, such as the International Pediatric Adrenocortical Tumor Registry, is needed to collect sufficient data to better guide our clinical management.
 ...
PMID:Adrenocortical tumors and hyperplasias in childhood--etiology, genetics, clinical presentation and therapy. 1702 81

Adrenal cortical neoplasms in pediatric patients are rare. The clinical manifestations and biologic behavior of these tumors can be quite distinct from their histologically similar counterparts in the adult population. We report 5 cases of adrenocortical neoplasms in young children and review their clinical presentations, pathology, and follow-up data. Pathologic evaluations included histology and immunostains with p53 and Ki-67. The patients were 3 girls and 2 boys, 13-28 mo of age. The patients all presented with virilization and other hormone-related symptoms for an average duration of 6 mo. Serum testosterone levels were elevated in 3 cases. Imaging studies revealed neoplasms in the left adrenal gland in 3 cases and the right adrenal gland in 2 cases. No evidence of disease was identified at any other site of the body. The tumors were grossly confined to the adrenal glands and ranged in diameter from 3 to 6 cm (mean 4.3 cm). Microscopically, the tumors had histological and immunophenotypic features characteristic of adrenocortical tumors. Additional features noted included capsular and/or vascular invasion, severe nuclear atypia, high mitotic rate (>15 mitotic figures/20 high power fields), and atypical mitotic figures. Necrosis was present in one case. Immunohistochemical staining indices for p53 and Ki-67 were >20%. After follow-up periods ranging from 5 mo to 9.5 yr, all patients were alive and free of disease. Despite histological and immunophenotypical evidence of malignancy, these localized adrenocortical neoplasms had a benign clinical course with no evidence of metastasis or recurrence. Age is an apparent prognostic factor as these patients were <3 yr old. Because of the discrepancy between pathology and clinical outcome, adrenocortical tumors in this age group should be classified as neoplasms of unknown malignant potential.
 ...
PMID:Adrenocortical neoplasms in young children: age as a prognostic factor. 1966 12

Childhood adrenocortical tumour (ACT) is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6%) or mixed with Cushing's syndrome (42.0%) was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate.
 ...
PMID:Childhood adrenocortical tumours: a review. 2022 12

Adrenocortical tumors in children are usually diagnosed because of signs of virilization and their prognosis is poor. They possess several distinct pathological features compared to adrenocortical tumors in adults and have an exceptional prevalence in southern Brazil, where they are nearly invariably linked to the presence of a germline specific TP53 (R337H) mutation. Other important factors in childhood adrenocortical tumor pathogenesis are overexpression of the Steroidogenic Factor-1 transcription factor and imprinting defects in the 11p15 genomic region, causing overexpression of Insulin-like Growth Factor-2. Genomic studies have revealed the prognostic relevance of the expression of some Major Histocompatibility Complex genes and the deregulation of the Insulin-like Growth Factor/mammalian Target Of Rapamycin pathway by microRNAs in these tumors. Our hope is that these findings will constitute the basis for the development of novel therapies that will be more active against these tumors and less toxic for the patients.
 ...
PMID:Genetics and genomics of childhood adrenocortical tumors. 2109 6


1 2 3 Next >>