Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression

Shigematsu, Kazuto; Nishida, Naoshi; Sakai, Hideki; Igawa, Tsukasa; Toriyama, Kan; Nakatani, Akira; Takahara, Osamu; Kawai, Kioko

doi:10.1530/eje-09-0596

Cited by 15 publications

(10 citation statements)

References 32 publications

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“…Case 5 displayed a negative staining for melan-A in both adenoma and peri-adenoma tissue, and a weakly positive staining for synaptophysin in adenoma and a negative staining for synaptophysin in peri-adenoma tissue, respectively. This immunostaining pattern was not consistent with that found in adrenals of patients with Cushing’s syndrome due to PPNAD [64, 65], while it has been reported in cortisol-secreting tumors or in APAs [66, 67]. …”

Section: Discussioncontrasting

confidence: 65%

Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series

et al. 2017

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Purpose Aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion are reported in an increasing number of patients. Five aldosterone-producing adenomas from patients with primary aldosteronism and subclinical hypercortisolism were examined. The aims of our study were: (1) to analyze pathological features and immunohistochemical expression of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) in these tumors; (2) to investigate somatic mutations involved in adrenal steroid hypersecretion and/or tumor growth. Methods Archival micro-dissected paraffin-embedded slides from tumor specimens were used for histological and molecular studies. Immunohistochemistry was performed using monoclonal anti-CYP11B1 and anti-CYP11B2 antibodies. Cellular composition was determined by examining for known features of zona fasciculata and zona glomerulosa, and immunoreactivity for CYP11B1 and CYP11B2 by McCarty H-score. Spot regions for mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, PRKACA, and CTNNB1 gene sequences were evaluated. Results Four APAs showed a predominant (≥50%) zona fasciculata-like cell pattern: one tumor had CYP11B1 H-score = 150, no detectable CYP11B2 expression, and harbored a PRKACA p.Leu206Arg mutation (that we have reported previously elsewhere), one had no CYP11B1 expression, CYP11B2 H-score = 40, and no mutations; the remaining two adenomas had high CYP11B1 H-score (160 and 240, respectively) and low CYP11B2 H-score (30 and 15, respectively), with the latter harboring a CTNNB1 p. Ser45Phe activating mutation. One of five aldosterone-producing adenomas had a predominant zona glomerulosa-like pattern, CYP11B1 H-score = 15, CYP11B2 H-score = 180, and no mutations. Conclusions The majority of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion were composed mainly of zona fasciculata-like cells, while CYP11B1 and CYP11B2 immunostaining demonstrated clear heterogeneity. In a subset of cases, different somatic mutations may be involved in hormone excess and tumor formation.

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Section: Discussioncontrasting

confidence: 65%

Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series

et al. 2017

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“…Along these lines, other neuroendocrine markers were tested in the current cases (as well as in the fetal normal glands), including chromogranin A, synapsin, CD57 and CD56. Only the latter was found positive in all tested cases, but it is known that CD56 is highly expressed in normal adrenal cortex and derived tumors (22,24). It is worth noting, however, that in focally myxoid tumors the expression of neurofilaments and CD56 was mostly restricted to the myxoid areas.…”

Section: Discussionmentioning

confidence: 83%

Adrenocortical Tumors With Myxoid Features: A Distinct Morphologic and Phenotypical Variant Exhibiting Malignant Behavior

Papotti

Volante

Duregon

et al. 2010

American Journal of Surgical Pathology

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Myxoid changes have been rarely reported both in adrenocortical adenomas and carcinomas. The recent observation by our group of an adrenal myxoid tumor with morphologically borderline features but aggressive clinical behavior prompted us to review a series of 196 adrenocortical lesions, comprising 122 carcinomas and 74 adenomas, to define the morphological, phenotypical and clinical characteristics of adrenocortical tumors with myxoid features. Fourteen cases, including 12 carcinomas and 2 borderline tumors, formed the basis of this report, and were characterized by a variably abundant myxoid component (from 5% to 90% of tumor) and two distinct cellular growth patterns: the first (10 cases), mostly associated with a predominant myxoid stromal component, was made of small cells with mild atypia arranged in cords and microcysts; the second (4 cases) was characterized by focal myxoid changes in tumors otherwise similar to conventional adrenocortical carcinoma, with large atypical cells having an eosinophilic cytoplasm and a diffuse or nodular architecture. The above mentioned patters were absent in all adenomas reviewed. A peculiar reactivity to neurofilaments was seen, mostly associated to the presence of predominant rather that focal myxoid stromal changes, as well as in 40% of conventional adrenocortical carcinomas, thus representing an undescribed potential pitfall in the differential diagnosis of adrenal lesions. Myxoid adrenocortical tumors probably represent a rare but histologically and phenotipically distinct entity and, although rare cases of benign lesions are on record, they seem to be generally associated to morphological and clinical features of malignancy.

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“…Sections were then incubated in PBS-TX-BSA and 0.1% sodium azide for 48 h at 4°C with either mouse anti-TH (1:5000, Immunostar) or rabbit anti-TH (1:2000, Millipore) and mouse anti-synaptophysin (1:75000, clone SY38, Millipore). Specificity of the anti-synaptophysin antibody has been characterized previously using a preabsorption control [39]. Sections incubated in anti-TH antibody alone were rinsed (PBS-TX-BSA) three times over 30 min and incubated in donkey anti-mouse antibody conjugated to Alexa Flour 488 (1:200, Invitrogen) for 90 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Sexual dimorphism in locus coeruleus dendritic morphology: A structural basis for sex differences in emotional arousal

Bangasser

Zhang

Garachh

et al. 2011

Physiology & Behavior

116

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Stress-related psychiatric disorders, such as depression and anxiety, affect a disproportionate number of women. We previously demonstrated that the major brain norepinephrine (NE)-containing nucleus, locus coeruleus (LC) is more sensitive to stressors and to the stress-related neuropeptide, corticotropin-releasing factor (CRF) in female compared to male rats. Because the LC-NE system is a stress-responsive system that is thought to be dysregulated in affective disorders, sex differences in LC structure or function could play a role in female vulnerability to these diseases. The present study used different approaches to compare LC dendritic characteristics between male and female rats. Immunofluorescence labeling of tyrosine hydroxylase, the norepinephrine synthetic enzyme, revealed that LC dendrites of female rats extend further into the peri-LC region, covering a significantly greater area than those of males. Optical density measurements of dendrites in the peri-LC revealed increased dendritic density in females compared to their male counterparts. Additionally, immunoreactivity for synaptophysin, a synaptic vesicle protein, was significantly greater in the LC in female rats, suggesting an increased number of synaptic contacts onto LC processes. Individual LC neurons were juxtacellularly labeled with neurobiotin in vivo for morphological analysis. LC dendritic trees of females were longer and had more branch points and ends. Consistent with this, Sholl analysis determined that, compared to males, LC dendrites of females had a more complex pattern of branching. The greater dendritic extension and complexity seen in females predicts a higher probability of communication with diverse afferents that terminate in the peri-LC. This may be a structural basis for heightened arousal in females, an effect which may, in part, account for the sex bias in incidence of stress-related psychiatric disorders.

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Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression

Cited by 15 publications

References 32 publications

Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series

Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series

Adrenocortical Tumors With Myxoid Features: A Distinct Morphologic and Phenotypical Variant Exhibiting Malignant Behavior

Sexual dimorphism in locus coeruleus dendritic morphology: A structural basis for sex differences in emotional arousal

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