Adrenocortical Carcinoma: A malignant neoplasm of the ADRENAL CORTEX. Adrenocortical carcinomas are unencapsulated anaplastic (ANAPLASIA) masses sometimes exceeding 20 cm or 200 g. They are more likely to be functional than nonfunctional, and produce ADRENAL CORTEX HORMONES that may result in hypercortisolism (CUSHING SYNDROME); HYPERALDOSTERONISM; and/or VIRILISM.Adrenal Cortex Neoplasms: Tumors or cancers of the ADRENAL CORTEX.Mitotane: A derivative of the insecticide DICHLORODIPHENYLDICHLOROETHANE that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression.Adrenocortical Adenoma: A benign neoplasm of the ADRENAL CORTEX. It is characterized by a well-defined nodular lesion, usually less than 2.5 cm. Most adrenocortical adenomas are nonfunctional. The functional ones are yellow and contain LIPIDS. Depending on the cell type or cortical zone involved, they may produce ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and/or ANDROSTENEDIONE.Adrenal Cortex: The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN.Carcinoma: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)Cushing Syndrome: A condition caused by prolonged exposure to excess levels of cortisol (HYDROCORTISONE) or other GLUCOCORTICOIDS from endogenous or exogenous sources. It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of ADRENOCORTICOTROPIN and those that are ACTH-independent.Adrenal Gland Neoplasms: Tumors or cancer of the ADRENAL GLANDS.Adrenocorticotropic Hormone: An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Myelolipoma: A rare benign tumor of the adrenal gland, several centimeters in diameter, composed in varying proportions of adipose tissue, lymphocytes, and primitive myeloid cells, probably a developmental abnormality. (Dorland, 27th ed)Adrenal Glands: A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.Adrenal Rest Tumor: Neoplasm derived from displaced cells (rest cells) of the primordial ADRENAL GLANDS, generally in patients with CONGENITAL ADRENAL HYPERPLASIA. Adrenal rest tumors have been identified in TESTES; LIVER; and other tissues. They are dependent on ADRENOCORTICOTROPIN for growth and adrenal steroid secretion.Adrenalectomy: Excision of one or both adrenal glands. (From Dorland, 28th ed)Steroid 17-alpha-Hydroxylase: A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.Carcinoma, Squamous Cell: A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)Adrenal Cortex Diseases: Pathological processes of the ADRENAL CORTEX.Carcinoma, Hepatocellular: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.Adenoma: A benign epithelial tumor with a glandular organization.Feminization: Development of female secondary SEX CHARACTERISTICS in the MALE. It is due to the effects of estrogenic metabolites of precursors from endogenous or exogenous sources, such as ADRENAL GLANDS or therapeutic drugs.Adrenocortical Hyperfunction: Excess production of ADRENAL CORTEX HORMONES such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and/or ANDROSTENEDIONE. Hyperadrenal syndromes include CUSHING SYNDROME; HYPERALDOSTERONISM; and VIRILISM.17-Ketosteroids: Steroids that contain a ketone group at position 17.17-alpha-Hydroxyprogesterone: A metabolite of PROGESTERONE with a hydroxyl group at the 17-alpha position. It serves as an intermediate in the biosynthesis of HYDROCORTISONE and GONADAL STEROID HORMONES.Li-Fraumeni Syndrome: Rare autosomal dominant syndrome characterized by mesenchymal and epithelial neoplasms at multiple sites. MUTATION of the p53 tumor suppressor gene, a component of the DNA DAMAGE response pathway, apparently predisposes family members who inherit it to develop certain cancers. The spectrum of cancers in the syndrome was shown to include, in addition to BREAST CANCER and soft tissue sarcomas (SARCOMA); BRAIN TUMORS; OSTEOSARCOMA; LEUKEMIA; and ADRENOCORTICAL CARCINOMA.Endocrine Surgical Procedures: Surgery performed on any endocrine gland.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Aldosterone: A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.Steroidogenic Factor 1: A transcription factor and member of the nuclear receptor family NR5 that is expressed throughout the adrenal and reproductive axes during development. It plays an important role in sexual differentiation, formation of primary steroidogenic tissues, and their functions in post-natal and adult life. It regulates the expression of key steroidogenic enzymes.3-Hydroxysteroid Dehydrogenases: Catalyze the oxidation of 3-hydroxysteroids to 3-ketosteroids.Adrenal Cortex HormonesTumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Aromatase: An enzyme that catalyzes the desaturation (aromatization) of the ring A of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the CYP19 gene, and functions in complex with NADPH-FERRIHEMOPROTEIN REDUCTASE in the cytochrome P-450 system.Cell Line, Tumor: A cell line derived from cultured tumor cells.Carcinoma in Situ: A lesion with cytological characteristics associated with invasive carcinoma but the tumor cells are confined to the epithelium of origin, without invasion of the basement membrane.Dehydroepiandrosterone: A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.Steroids: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)Tomography, X-Ray Computed: Tomography using x-ray transmission and a computer algorithm to reconstruct the image.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Incidental Findings: Unanticipated information discovered in the course of testing or medical care. Used in discussions of information that may have social or psychological consequences, such as when it is learned that a child's biological father is someone other than the putative father, or that a person tested for one disease or disorder has, or is at risk for, something else.Carcinoma, Papillary: A malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. (Stedman, 25th ed)Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Antineoplastic Agents, Hormonal: Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)Neoplasm Staging: Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Retroperitoneal NeoplasmsInhibins: Glycoproteins that inhibit pituitary FOLLICLE STIMULATING HORMONE secretion. Inhibins are secreted by the Sertoli cells of the testes, the granulosa cells of the ovarian follicles, the placenta, and other tissues. Inhibins and ACTIVINS are modulators of FOLLICLE STIMULATING HORMONE secretions; both groups belong to the TGF-beta superfamily, as the TRANSFORMING GROWTH FACTOR BETA. Inhibins consist of a disulfide-linked heterodimer with a unique alpha linked to either a beta A or a beta B subunit to form inhibin A or inhibin B, respectivelyGene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from DEATH, the physiological cessation of life and from MORTALITY, an epidemiological or statistical concept.
Adrenocortical carcinomaAdrenocortical adenoma: A adrenocortical adenoma (or adrenal cortical adenoma) is a benign tumor of the adrenal cortex.Anaplastic carcinoma: Anaplastic carcinoma is a general term for a malignant neoplasm arising from the uncontrolled proliferation of transformed cells of epithelial origin, or showing some epithelial characteristics, but that reveal no cytological or architectural features of associated with more differentiated tumors, such as the glandular formation or special cellular junctions that typical of adenocarcinoma and squamous cell carcinoma, respectively.Cushing reflex: Cushing reflex (also referred to as the vasopressor response, the Cushing effect, the Cushing reaction, the Cushing phenomenon, the Cushing response, or Cushing's Law) is a physiological nervous system response to increased intracranial pressure (ICP) that results in Cushing's triad of increased blood pressure, irregular breathing, and a reduction of the heart rate. It is usually seen in the terminal stages of acute head injury and may indicate imminent brain herniation.Adrenal tumorAlcohol and cortisol: Recent research has looked into the effects of alcohol on the amount of cortisol that is produced in the human body. Continuous consumption of alcohol over an extended period of time has been shown to raise cortisol levels in the body.MyelolipomaAbsent adrenal glandSquamous-cell carcinomaFibrolamellar hepatocellular carcinomaThyroid adenomaFeminisation of the workplace: In response to the pressure from feminism and cultural trends highlighting characteristics in workers which have culturally been associated with women, feminisation of the workplace is a label given to the trend towards greater employment of women, and of men willing and able to operate with these more 'feminine' modes of interaction.Adrenocortical hyperfunctionGeorge J. ZimmermannLi–Fraumeni syndromeNami Matsuda: was a Christian Japanese female physician who worked at Kikuchi Keifuen Sanatorium, Okinawa Airakuen Sanatorium and Hoshizuka Keiaien Sanatorium. In 1945, she was the head doctor under the director and survived extremely dreadful battles with 7 nurses which included chief nurse Chiyo Mikami at Okinawa Airakuen Sanatorium.Aldosterone escape: In physiology, aldosterone escape is a term that has been used to refer to two distinct phenomena involving aldosterone that are exactly opposite each other:Cancer biomarkers: A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer.Aromatase deficiency: Aromatase deficiency is a condition resulting from insufficient production of the enzyme aromatase, which can lead to inappropriate virilization in females.Steroid use in Bollywood: The use of steroids by Bollywood actors has become highlighted in a number of newspaper and web articles where actors and models with previously very thin physiques have in a short period of time developed muscular bodies.Dense artery sign: In medicine, the dense artery sign or hyperdense artery sign is a radiologic sign seen on computer tomography (CT) scans suggestive of early ischemic stroke. In earlier studies of medical imaging in patients with strokes, it was the earliest sign of ischemic stroke in a significant minority of cases.Incidentaloma: In medicine, an incidentaloma is a tumor ([found by coincidence (incidentally) without clinical symptom]s or suspicion. Like other types of [[incidental findings, it is found during the course of examination and imaging for other reasons.ABCD rating: ABCD rating, also called the Jewett staging system or the Whitmore-Jewett staging system, is a staging system for prostate cancer that uses the letters A, B, C, and D.Mature messenger RNA: Mature messenger RNA, often abbreviated as mature mRNA is a eukaryotic RNA transcript that has been spliced and processed and is ready for translation in the course of protein synthesis. Unlike the eukaryotic RNA immediately after transcription known as precursor messenger RNA, it consists exclusively of exons, with all introns removed.Gross examination
(1/185) YM116, 2-(1H-imidazol-4-ylmethyl)-9H-carbazole, decreases adrenal androgen synthesis by inhibiting C17-20 lyase activity in NCI-H295 human adrenocortical carcinoma cells.
The concentrations of androstenedione and dehydroepiandrosterone, products of C17-20 lyase, in the medium after a 6-hr incubation of NCI-H295 cells were decreased by YM116 (2-(1H-imidazol-4-ylmethyl)-9H-carbazole) (IC50: 3.6 and 2.1 nM) and ketoconazole (IC50: 54.9 and 54.2 nM). 17Alpha-hydroxyprogesterone, a product of 17alpha-hydroxylase, was increased by YM116 (1-30 nM) and by ketoconazole (10-300 nM) and then was decreased at higher concentrations of both agents (IC50: 180 nM for YM116, 906 nM for ketoconazole), indicating that YM116 and ketoconazole were 50- and 16.5-fold more specific inhibitors of C17-20 lyase, respectively, than 17alpha-hydroxylase. Compatible with these findings, progesterone, a substrate of 17alpha-hydroxylase, was increased by these agents. Cortisol production was inhibited by YM116 and ketoconazole (IC50: 50.4 and 80.9 nM, respectively). YM116 was a 14-fold more potent inhibitor of androstenedione production than cortisol production, whereas ketoconazole was a nonselective inhibitor of the production of both steroids. YM116 and ketoconazole inhibited the C17-20 lyase activity in human testicular microsomes (IC50: 4.2 and 17 nM, respectively). These results demonstrate that YM116 reduces the synthesis of adrenal androgens by preferentially inhibiting C17-20 lyase activity. (+info)
(2/185) Comparison of expression and regulation of the high-density lipoprotein receptor SR-BI and the low-density lipoprotein receptor in human adrenocortical carcinoma NCI-H295 cells.
In rodents, cholesterol for adrenal steroidogenesis is derived mainly from high-density lipoproteins (HDL) via the HDL receptor, scavenger receptor-BI (SR-BI). In humans cholesterol for steroidogenesis is considered to be derived from the low-density lipoprotein (LDL) receptor pathway, and the contribution of SR-BI to that is unknown. In the present study SR-BI expression and regulation by steroidogenic stimuli was analysed in human adrenocortical cells and compared with LDL receptor expression. In addition, the functional contribution of both receptors for cholesteryl ester delivery to human adrenocortical cells was compared. Northern blot and reverse transcription-PCR amplification and sequence analysis demonstrated the presence of SR-BI mRNA in foetal and adult human adrenal cortex. Furthermore, SR-BI mRNA was expressed to similar levels in human primary adrenocortical and adrenocortical carcinoma NCI-H295 cells, indicating its presence in the steroid-producing cells. Treatment of NCI-H295 cells with 8Br-cAMP, a stimulator of glucocorticoid synthesis via the protein kinase A second messenger signal transduction pathway, resulted in an increase of both SR-BI and LDL receptor mRNA levels in a time- and dose-dependent manner. The induction of SR-BI and LDL receptor by cAMP was independent of ongoing protein synthesis and occurred at the transcriptional level. Ligand blot experiments indicated that a protein of similar size to SR-BI is the major HDL-binding protein in NCI-H295 cells. Western blot analysis demonstrated that cAMP treatment increased the levels of LDL receptor and, to a lesser extent, SR-BI protein in NCI-H295 cells. Binding and uptake of cholesterol was quantitatively smaller from HDL than from LDL, both in basal as well as in cAMP-stimulated cells. Scatchard analysis under basal conditions indicated that NCI-H295 cells express twice as many specific binding sites for LDL than for HDL. Dissociation constant values (Kd; in nm) were approximately five times higher for HDL than for LDL, indicating a lower affinity of HDL compared with LDL. The combined effects of these two parameters and the low cholesteryl ester content of HDL subfraction 3 (HDL3) contributes to a lower cholesteryl ester uptake from HDL than from LDL by the NCI-H295 cells. In conclusion, both the SR-BI and LDL receptor genes are expressed in the human adrenal cortex and coordinately regulated by activators of glucocorticoid synthesis. In contrast to rodents, in human adrenocortical cells the HDL pathway of cholesterol delivery appears to be of lesser importance than the LDL pathway. Nevertheless, the SR-BI pathway may become of major importance in conditions of functional defects in the LDL receptor pathway. (+info)
(3/185) The expression of inhibin/activin subunits in the human adrenal cortex and its tumours.
Inhibins and activins are dimeric proteins of the transforming growth factor-beta superfamily which have been shown to be expressed in the adrenal cortex. Recent studies have suggested a role for these peptides in the pathogenesis and/or function of adrenal tumours. To investigate further their physiological and pathological roles, we have documented immunoreactivity for inhibin alpha, betaA and betaB subunits in normal adult and fetal human adrenals, in hyperplastic adrenals and in adrenal tumours. In the normal and hyperplastic adult gland, diffuse immunopositivity was demonstrated for beta subunits, suggesting that activins (beta beta dimers) can be expressed in all zones. Inhibin alpha was limited to the zona reticularis and the innermost zona fasciculata in the normal gland, extending centripetally into the zona fasciculata in hyperplasia, supporting a role for ACTH in the regulation of expression, and suggesting that expression of inhibins (alpha beta dimers) is restricted. Immunopositivity for all three subunits was seen in both fetal and definitive zones of the fetal cortex, indicating that both inhibins and activins could be expressed in both. Immunopositivity for all three subunits was seen in most adrenocortical tumours. Loss of immunopositivity for inhibin alpha in a subgroup of carcinomas might indicate a role in tumour progression. The greater intensity of staining for inhibin alpha in tumours associated with Cushing's syndrome again suggests a link with cortisol production. (+info)
(4/185) Autocrine role of IGF-II in proliferation of human adrenocortical carcinoma NCI H295R cell line.
In adrenocortical tumors, the malignant phenotype is associated with rearrangements (paternal isodisomy) at the 11p15 locus and IGF-II gene overexpression, strongly suggesting that the IGF system is a major determinant of adrenocortical tumor progression. The aim of this study was to validate an in vitro model for investigating the involvement of the IGF system in adrenocortical tumorigenesis. We analyzed the production of IGF mRNA and proteins, IGF-binding proteins (IGFBPs) and IGF receptors by the NCI H295R cell line, which is derived from a human adult adrenocortical carcinoma. H295R cells were shown to proliferate for a long period (26 days) in the absence of serum or any added growth factor. Northern blot analyses showed high IGF-II mRNA contents in H295R cells. The cells secreted large amounts of IGF-II protein (14 ng/10(6) cells per 48 h) although no IGF-I protein was detected. Western ligand blot analyses of conditioned media detected the presence of large amounts of a 34 kDa protein, which was identified as IGFBP-2 by immunoblotting. The presence of high-affinity binding sites for IGF-I and IGF-II on H295R cells was shown by binding experiments using radiolabeled IGFs and confirmed by reverse transcription PCR analyses showing type 1 and type 2 IGF receptors. Proliferation of H295R cells was inhibited by anti-IGF-II antibody (45%) and by anti-type 1 IGF receptor antibody (53%) indicating that IGF-II is an autocrine growth factor for these cells and that its effects are, at least in part, mediated by the type 1 IGF receptor. These findings confirm the involvement of the IGF system in adrenocortical tumors and suggest that the H295R cell line is a suitable in vitro model for studying the molecular mechanisms of adrenocortical tumor proliferation. (+info)
(5/185) Lack of response to octreotide in Cushing's syndrome due to metastatic adrenocortical carcinoma.
Functional metastatic adrenocortical carcinoma is an uncommon cause of Cushing's syndrome, which rarely responds to conventional treatment. A patient presenting with Cushing's syndrome secondary to adrenocortical carcinoma underwent surgical resection. Postoperatively, she developed metastatic disease resistant to conventional chemotherapy. Octreotide, a somatostatin analogue which is effective in the treatment of several types of neuroendocrine tumour, was tried to ameliorate her secretory symptoms, but without any therapeutic effect. (+info)
(6/185) Analysis of genomic alterations in sporadic adrenocortical lesions. Gain of chromosome 17 is an early event in adrenocortical tumorigenesis.
Genetic changes underlying the tumorigenesis of sporadic adrenocortical tumors are poorly characterized. To search for characteristic genomic imbalances involved in adrenocortical tumors, we examined 41 adrenocortical lesions (12 carcinomas, 23 adenomas, and 6 hyperplasias) by comparative genomic hybridization. Our results show that genetic alterations are more frequent in malignant than in benign lesions and that they rarely occur in hyperplastic lesions. The most frequent DNA copy number changes in adrenocortical carcinomas included losses of 1p21-31, 2q, 3p, 3q, 6q, 9p, and 11q14-qter, as well as gains and amplifications of 5q12, 9q32-qter, 12q, and 20q. The genomic aberrations prevalently occurring in adrenocortical adenomas were gains of 17q, 17p, and 9q32-qter. Gains found in 2 of 6 adrenocortical hyperplastic lesions involved chromosome 17 or 17q only. These data indicate that oncogenes determining the early tumorigenesis of adrenocortical tumors may exist on chromosome 17 and that the number of genomic alterations is closely associated with tumor behavior in adrenocortical tumors. (+info)
(7/185) Changes in neoplastic cell features and sensitivity to mitotane during mitotane-induced remission in a patient with recurrent, metastatic adrenocortical carcinoma.
A 58-year-old man had adrenocortical carcinoma in the right adrenal gland. The tumour secreted excessive cortisol and dehydroepiandrosterone-sulphate (DHEA-S), and had invaded the right hepatic lobe and vena cava. Eleven months after surgical tumour resection, the serum DHEA-S levels again increased. Local tumour recurrence and a metastasis was found in the lung. Eleven months after surgery chemotherapy with mitotane (o,p'-DDD) was initiated. Twelve weeks of mitotane reduced serum DHEA-S levels and caused these tumours to disappear. The patient was then treated with low-dose mitotane (1.5-2.0 g/day) for 2 years. Serum levels of mitotane remained at less than 10 microg/ml. Although such low serum levels of mitotane and delayed initiation of mitotane after surgery have been proposed to weaken the antineoplastic effect of mitotane, the patient had a remission for 2 years. However, there was then local re-recurrence with an increase in serum DHEA-S and death 4 months later. The histological features of neoplastic cells were quite different comparing tumour resected at surgery and tumour at autopsy. The latter had more frequent mitotic nuclei. This tumour was initially sensitive to mitotane, but later became insensitive. (+info)
(8/185) Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm.
Inhibins are gonadal glycoprotein hormones whose main endocrine function is to inhibit pituitary FSH secretion. In addition to testes and ovaries, other steroid-producing organs are sites of inhibin alpha subunit expression. To study the role of inhibins in human adrenal gland, we screened a panel of 150 adrenals (10 normal adrenals, 25 adrenocortical hyperplasias, 65 adrenocortical adenomas, 30 adrenocortical carcinomas and 20 phaeochromocytomas) for inhibin alpha expression. mRNA levels of inhibin alpha subunit were studied in 57 samples and all tissues were stained immunohistochemically with an inhibin alpha subunit-specific antibody. Inhibin alpha mRNA was detected in all adrenocortical tissues. Virilizing adenomas possessed a 10-fold higher median inhibin alpha mRNA expression than did normal adrenals. Bilaterally and nodularly hyperplastic adrenals and other than virilizing adrenocortical tumours had their median inhibin alpha mRNA levels close to those of normal adrenals. Immunohistochemically, inhibin alpha subunit was detectable in all normal and hyperplastic adrenals, as well as in 73% of the adrenocortical tumours. However, the percentage of inhibin alpha-positive cells varied greatly in different tumour types. The median percentage of positive cells was 10 in non-functional and Conn's adenomas, 30 in Cushing's adenomas and 75 in virilizing adenomas. In malignant adrenocortical tumours the median percentage of inhibin alpha-immunopositive cells was 20 in non-functional carcinomas, 30 in Conn's carcinomas, 65 in Cushing's carcinomas and 75 in virilizing carcinomas. All phaeochromocytomas were negative for inhibin alpha subunit both at the mRNA level and immunohistochemically. Our data show that inhibin alpha subunit is highly expressed in both normal and neoplastic androgen-producing adrenocortical cells, with less expression in cortisol-producing and hardly any in aldosterone-producing cells. This suggests a specific role for inhibins in the regulation of adrenal androgen production. We did not find any significant difference in inhibin alpha expression between benign and malignant adrenocortical tumours. Thus inhibin alpha gene does not seem to have a tumour suppressor role in human adrenal cortex. (+info)
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