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1.
Scheithauer BW Kovacs K Zorludemir S Lloyd RV Erdogan S Slezak J 《Endocrine pathology》2008,19(1):27-33
Little information is available regarding androgen receptor immunoexpression (AR) in the normal and neoplastic human pituitary.
Available experimental data links it to primarily gonadotroph cells. We undertook an immunohistochemical study of 41 autopsy-derived
normal glands from patients of both sexes and all ages as well as 79 fully characterized pituitary adenomas of all types,
the focus being upon AR expression in normal and neoplastic gonadotrophs. Nuclear AR immunoreactivity was noted in gonadotrophs
and other normal adeno- and neurohypophysial cells. In addition to its presence in 74% of gonadotroph and 55% of null cell
adenomas, lesser proportions of other adenoma types (adrenocorticotropic hormone 50%, prolactin 38%, growth hormone 33%) also
exhibited AR immunoreactivity. No staining of thyroid-stimulating hormone adenomas was noted. The physiologic significance
of our findings remains to be explored. The literature regarding AR expression in animal and human pituitaries is reviewed. 相似文献
2.
Thapar K Yamada Y Scheithauer B Kovacs K Yamada S Stefaneanu L 《Endocrine pathology》1996,7(3):215-221
Assessment of mitotic activity represents one of the oldest and most routinely used histopathologic methods of evaluating
the biological aggressiveness of human tumors. In the case of pituitary tumors, however, the relevance of this approach as
a means of gaging tumor behavior remains ill-defined. In this article, the relationship between the mitotic index and biological
aggressiveness of pituitary tumors was evaluated in a series of 54 pituitary adenomas and 6 primary pituitary carcinomas.
All tumors were fully classified by immunohistochemistry and electron microscopy; adenomas were further stratified on the
basis of their invasion status, the latter being defined as gross, operatively, or radiologically apparent infiltration of
dura or bone. Mitotic figures were present in 11 tumors, 10 being either invasive adenomas or pituitary carcinomas. A significant
association between the presence of mitotic figures and tumor behavior was noted, as evidenced by progressive increments in
the proportion of cases expressing mitotic figures in the categories of noninvasive adenoma, invasive adenoma, and pituitary
carcinoma (3.9, 21.4, and 66.7%, respectively; Fisher’s exact test, two-tailed,p<0.001). The mitotic index, however, appeared to be a less informative parameter, being extremely low in all cases (mean=0.016%±0.005
[±SEM]). Although the mean mitotic index in pituitary carcinomas (0.09%±0.035) was significantly higher than the mean mitotic
index of either noninvasive adenomas (0.002%±0.002) or invasive adenomas (0.013%±0.005), no practical threshold value capable
of distinguishing these three groups was evident. Comparison of the mitotic index with Ki-67 derived growth fractions in these
tumors revealed a significant but weak linear correlation (r=0.41,p<0.01). These data suggest that when, mitotic figures are present, they do provide some indication of the behavior and invasive
potential of pituitary tumors. For routine diagnostic purposes, however, the discriminating power of this parameter is somewhat
limited, being superseded by alternative and more informative methods of growth fraction determination such as that provided
by the Ki-67 immunolabeling. 相似文献
3.
Epidermal growth factor (EGF) and epidermal growth factor receptor (EGFr) were investigated by immunocytochemistry (ICH) in
57 human pituitary adenomas and 10 nontumorous autopsy pituitaries. EGF immunoreactivity was demonstrated in 24 adenomas (42%),
representing 23 functioning tumors and 1 nonfunctioning tumor of oncocytic type, and in all nontumorous pituitaries. Among
40 tumors, EGFr was found positive in 15 functioning adenomas (37.5%), representing 50% of them. The presence of both EGF
and EGFr was found mainly in corticotroph adenomas (60%) and less frequently in somatotroph and lactotroph adenomas (20%).
ICH on serial sections with EGF or EGFr and adrenocorticotrophic hormone (ACTH) or S-100 protein revealed that EGF and EGFr
are localized specifically in corticotrophs and EGFr in stellate cells of nontumorous adenohypophysis.
These results confirm the presence of EGF and EGFr in human pituitary adenomas and nontumorous pituitaries and highlight their
frequent occurrence in hormone-producing adenomas. Further work is required to explore the possibility that EGF and EGFr play
a role in hormone production, release, and tumor progression. 相似文献
4.
5.
Maxwell Sehested Klaus Hou-Jensen 《Virchows Archiv : an international journal of pathology》1981,391(2):217-225
Summary The presence and distribution of Factor VIII related antigen (FVIIIR:Ag) in formalin fixed, paraffin embedded tissue were studied in benign and malignant vascular tumors, inflammatory vascular diseases, normal tissue from various organs and a number of malignant tumors. The unlabeled peroxidase-anti-peroxidase method was utilized. Immunostaining was observed only in endothelial cells, in tumor cells of endothelial cell origin and in megakaryocytes and platelets. The staining method gave a distinct picture of the vascular pattern in all types of tissue examined. The demonstration of FVIIIR: Ag by means of the immunoperoxidase technique is considered a valuable method in diagnosing tumors of vascular origin. The method also facilitates detection of vascular invasion of malignant tumors in small caliber vessels. 相似文献
6.
Vascular Endothelial Growth Factor (VEGF) Expression in Human Pituitary Adenomas and Carcinomas 总被引:4,自引:0,他引:4
Lloyd RV Scheithauer BW Kuroki T Vidal S Kovacs K Stefaneanu L 《Endocrine pathology》1999,10(3):229-235
Vascular endothelial growth factor (VEGF) is a key mediator of endothelial cell proliferation, angiogenesis, and vascular
permeability. Little is known about its expression in human pituitary adenomas.
We examined 148 human pituitary adenomas for VEGF protein expression by immunohistochemistry. The strongest immunoreactivity
was present in GH adenomas, corticotroph, silent corticotroph, silent subtype 3, and nononcocytic null cell adenomas. GH adenomas
treated with octreotide strained less intensely than did untreated tumors. Relatively weak staining was present in PRL, gonadotroph,
thyrotroph, and oncocytic null cell adenomas in the same sections showed evidence of down-regulation of VEGF protein expression
in adenomas. Pituitary carcinomas usually had stronger staining than adenomas.
In situ hybridization studies with oligonucleotide probes showed positive staining in all groups with stronger staining in
GH, ACTH, TSH, and gonadotroph adenomas and in pituitary carcinomas.
These results indicate that VEGF expression is more prominent in certain adenoma subtypes, that decreased expression occurs
in adenomas as compared to nontumorous pituitary and that carcinomas show increased VEGF expression relative to adenomas suggesting
up-regulation of VEGF during pituitary tumor progression. 相似文献
7.
La Rosa S Uccella S Dainese L Marchet S Placidi C Vigetti D Capella C 《Endocrine pathology》2008,19(2):104-111
c-kit (CD117) is a tyrosine kinase receptor involved in the proliferation, differentiation, and secretory functions of various cells. In experimental animal models, c-kit has been detected in the pars intermedia of the normal pituitary gland and in alpha-melanocyte-stimulating-hormone-positive adenomas and it has been suggested that it plays a role in regulating adrenocorticotropic hormone (ACTH) secretion. To the best of our knowledge, the expression of c-kit in normal human pituitary cells and in pituitary adenomas has never been reported, so the possible biological role of this receptor in the control of pituitary hormone secretion remains unclear. The aim of this study was to evaluate the immunohistochemical expression of c-kit in normal human pituitary glands and in a series of 62 well-characterized pituitary adenomas. In normal adenohypophyses, several cells, mainly located in the central mucoid wedge, showed a c-kit immunoreactivity (IR). Double label immunostaining procedures showed that the c-kit-IR cells corresponded to ACTH cells. Out of 62 adenomas, 15 (24%) were c-kit-IR, including 7/16 (44%) ACTH cell, 3/7 (42%) null cell, 4/11 (36%) alpha-subunit cell, and 1/11 (10%) follicle-stimulating hormone-luteinizing hormone cell adenomas. By contrast, all ten prolactin cell and seven growth hormone cell adenomas were c-kit negative. These data suggest that, in normal conditions, c-kit may be involved in the pituitary-adrenal axis regulation. 相似文献
8.
Ectopic pituitary adenoma (EPA) is rare and, to the authors’ knowledge, its association with peliosis has not yet been described.
The case of a 38-yr-old woman with clinical and biochemical evidence of Cushing’s syndrome is reported. Magnetic resonance
imaging (MRI) disclosed a normal pituitary and a separate mass in the sphenoid sinus. The surgically remove’s hyaline change
in the corticotrophs, indicating exposure to glucocorticoid excess. By histology, the mass in the sphenoid sinus was a congested,
chromophobic, partly basophilic, periodic acid-Schiff (PAS)-positive pituitary adenoma composed of pleomorphic, adrenocorticotropic
hormone (ACTH)-positive, corticotrophs. There was focal immunopositivity for MIB-1 and proliferating cell nuclear antigen
(PCNA). Electron microscopy confirmed the diagnosis of corticotroph adenoma. A striking finding, consistent with the diagnosis
of peliosis, was the presence of multiple large blood-filled spaces lacking an endothelial lining. The capillaries were dilated,
but often appeared empty and the fenestrated endothelium exhibited discontinuities. The cause of peliosis is obscure. It may
be that the venous outflow was impaired in this case leading to capillary dilation, congestion, hyperpermeability, rupture,
and accumulation of blood in extravascular spaces. 相似文献
9.
Minematsu T Egashira N Kajiya H Takei M Takekoshi S Itoh Y Tsukamoto H Itoh J Sanno N Teramoto A Osamura RY 《Endocrine pathology》2007,18(1):8-15
The pituitary tumor-transforming gene (PTTG) is a homolog of yeast Securin, which arrests the activation of Separin to induce
sister chromatid separation in the transition from metaphase to anaphase. Pituitary tumor-transforming gene is also known
to induce angiogenesis during pituitary tumorigenesis. It has not been clarified whether PTTG functions as a cytoplasmic or
a nuclear protein. Our immunohistochemical study indicated that PTTG is localized in the cytoplasm of pituitary tumor cells.
In the present study, confocal laser scanning microscopy (CLSM) analysis of human pituitary adenomas and immunoelectron microscopy
of the mouse pituitary cell line, AtT-20, demonstrated the localization of PTTG in the Golgi apparatus and vesicles. Secreted
PTTG was detected by immunoblotting from culture medium of mouse pituitary tumor cell lines. Our results suggested that PTTG
is a secretory protein produced by pituitary tumor cells. In addition, PTTG may exert autocrine and/or paracrine functions
as a newly proposed important pathway for the action of PTTG. 相似文献
10.
Tomita T 《Endocrine pathology》1997,8(4):305-313
Matrix metalloproteinases (MMPs) are involved in remodeling processes and have been immunocytochemically localized in some
endocrine glands and their tumors. Using anterior pituitary gland and pituitary adenomas, immunocytochemical localization
of MMP-2 (gelatinase-A),-9 (gelatinase-B), tissue inhibitor of metalloproteinase (TIMP)-1 and-2 was performed. Normal anterior-pituitary
cells all contain MMPs and lesser amount of TIMPs, whereas far fewer MMPs and TIMPs are identified in anterior pituitary adenomas.
There is no correlation between pituitary hormone and MMPs-TIMPs localization, thus MMP-TIMP homeostasis may not be involved
in hormone synthesis and secretion of anterior pituitary cells and their adenomas. Because MMPs and TIMPs are more abundantly
and specifically localized in pituitary cells and their adenomas, MMPs and TIMPs may be included as markers for endocrine
cells, including anterior-pituitary cells. 相似文献
11.
Clusterin is a circulating multifunctional glycoprotein produced in several kinds of epithelial and neuronal cells. Clusterin
is upregulated during different physiological and pathological states, such as senescence, type-2 diabetes mellitus, Alzheimer
disease, and in various neoplasms. Herein, we investigated the immunohistochemical expression of clusterin in non-neoplastic
adenohypophysis of human autopsy subjects and pituitary adenomas. We also investigated the association of clusterin increase
with age in adenohypophysis of autopsy subjects. Immunohistochemically, clusterin was found positive in the cytoplasm of all
adenoma cases, and in the cytoplasm of parenchymal cells, stellate cells, mixed cell follicles and in colloidal material inside
of the follicles of non-neoplastic adenohypophysis as well. Clusterin expression in pituitary adenomas was found significantly
higher than in non-neoplastic adenohypophyses. In addition, in non-neoplastic adenohypophysis, a significant increase in clusterin
expression levels between young (≤30 years), middle aged (31 to 60 years), and older (≥61 years) subjects (p < 0.00001, analysis of variance [ANOVA]) was found. In addition to clusterin accumulation, presence of calcification (p < 0.045, ANOVA) and presence of large follicles with colloid accumulation (p < 0.004, ANOVA) were also statistically significant factors related to aging in non-neoplastic adenohypophysis. In conclusion,
the present study demonstrated that clusterin expression was found in non-neoplastic adenohypophysis and in upregulated amounts
in pituitary adenomas. This study also demonstrated that in non-neoplastic adenohypophyses, increase of clusterin positive
cells; histopathological findings of calcification or presence colloidal material accumulation in large follicles were associated
with age. To our knowledge, immunohistochemical localization of clusterin in pituitary adenomas was not reported previously. 相似文献
12.
13.
《Ultrastructural pathology》2013,37(2-3):171-183
The morphologic features of four pituitary adenomas, removed from 2 men and 2 women between 31 and 62 years of age, are reported. The tumors contained growth hormone (GH), prolactin (PRL), and one or more glycoprotein hormones–usually thyrotropin (TSH). Three tumors were associated with acromegaly and one with hyperprolactinemia. Hyperthyroidism was not evident in any of the patients. In the tumors of acromegalic subjects, GH-containing cells were the most numerous, whereas PRL cells were dominant in the adenoma accompanied by hyperprolactinemia. Electron microscopy revealed plurimorphous tumors comprised of various proportions of morphologically different cell types: densely granulated GH cells, TSH-like cells, and the less common mammosomatotrophs and PRL cells. It is suggested that pituitary adenomas producing GH, PRL, and glycoprotein hormones derive from the same precursor; their immunocytochemical profile, fine structural appearance, and endocrine function may depend on the degree and direction of the cellular differentiation. 相似文献
14.
Eva Horvath Kalman Kovacs Bernd W. Scheithauer Raymond V. Randall Edward R. Laws Jr Michael O. Thorner George T. Tindall Daniel L. Barrow 《Ultrastructural pathology》1983,5(2):171-183
The morphologic features of four pituitary adenomas, removed from 2 men and 2 women between 31 and 62 years of age, are reported. The tumors contained growth hormone (GH), prolactin (PRL), and one or more glycoprotein hormones-usually thyrotropin (TSH). Three tumors were associated with acromegaly and one with hyperprolactinemia. Hyperthyroidism was not evident in any of the patients. In the tumors of acromegalic subjects, GH-containing cells were the most numerous, whereas PRL cells were dominant in the adenoma accompanied by hyperprolactinemia. Electron microscopy revealed plurimorphous tumors comprised of various proportions of morphologically different cell types: densely granulated GH cells, TSH-like cells, and the less common mammosomatotrophs and PRL cells. It is suggested that pituitary adenomas producing GH, PRL, and glycoprotein hormones derive from the same precursor; their immunocytochemical profile, fine structural appearance, and endocrine function may depend on the degree and direction of the cellular differentiation. 相似文献
15.
The patterns of deposition and immunoreactivity of interstitial amyloid were studied in 11 pituitary glands obtained at autopsy
and 9 surgically resected pituitary adenomas using Congo red staining and a panel of antisera directed against 5 major amyloid
fibril proteins and all pituitary hormones. The deposition pattern of amyloid in pituitary glands differed from that in adenomas
but all amyloid deposits showed an immunostaining with anti-amyloid λ-light chain. The remaining antisera were immunonegative.In situ hybridization using an oligodeoxyribonucleotide-probe complementary to the mRNA coding for the constant region of human λ-light
chain yielded no hybridization signals in the pituitaries or pituitary adenomas, excluding local synthesis and secretion of
immunoglobulins. Since no case studied suffered from generalized Aλ-amyloidosis and adsorption of immunoglobulins to the unknown
amyloid fribril protein of the pituitary seems to be unlikely, crossreaction of the polyclonal antisera with an undefined
antigen is probable. The similar immunostaining properties of amyloid deposits in “normal” pituitaries and pituitary adenomas
suggest they both originate from the same precursor protein. 相似文献
16.
Primary Pituitary Lymphoma: A Histological, Immunohistochemical, and Ultrastructural Study with Literature Review 总被引:1,自引:0,他引:1
Olga Moshkin Paul Muller Bernd W. Scheithauer Jonathan Juco Eva Horvath Bruce J. Patterson Suzzane Kamel-Reid Kalman Kovacs 《Endocrine pathology》2009,20(1):46-49
We report the case of a 62-year-old man with headache and left sixth cranial nerve palsy. A computerized tomography scan revealed
an osteolytic process involving the sella turcica and clivus. A partial tumor resection was achieved via an endoscopic transsphenoidal
approach. Morphologic investigation revealed a diffuse large B cell lymphoma involving pituitary parenchyma. No systemic disease
was found upon staging. Primary pituitary lymphoma is extremely rare. An accurate histologic diagnosis is key to successful
treatment and a favorable prognosis. The literature is reviewed. 相似文献
17.
18.
Kovacs K Stefaneanu L Horvath E Buchfelder M Fahlbusch R Althoff PH Moore C 《Endocrine pathology》1996,7(1):91-97
A 64-year-old woman with long-standing Addison’s disease owing to destructive immune adrenalitis presented with hyperpigmentation
and progressively increasing blood adrenocorticotrophic hormone (ACTH) levels. Magnetic resonance imaging demonstrated a pituitary
microadenoma, which was removed by transsphenoidal surgery and investigated by histology, immunocytochemistry, transmission
electron microscopy, andin situ hybridization (ISH). The morphologic studies revealed a basophilic, periodic acid-Schiff (PAS)-positive pituitary adenoma
immunoreactive for ACTh and β-endorphin and in several cells for α-subunit. By transmission electron microscopy, the tumor
was a densely granulated corticotroph adenoma, which, by ISH, expressed pro-opiomelanocortin (POMC) mRNA. The lack of corticotroph
hyperplasia in the nontumorous adenohypophysis was an intriguing finding. Corticotroph adenomas in patients with long-standing
Addison’s disease were very rarely examined by morphology. Our report includes a detailed morphologic analysis and is the
first demonstration of POMC mRNA in the tumor cells using ISH. The question of whether the adenoma was related to increased
secretory activity secondary to protracted hypocorticism or developed independently unrelated to deranged endocrine homeostasis
remains unresolved. The lack of corticotroph hyperplasia in the nontumorous adenohypophysis favors the interpretation that
hypothalamic stimulation played no major role in adenoma formation in our case. 相似文献
19.
Pituitary Sex Steroid Receptors: Localization and Function 总被引:2,自引:0,他引:2
Stefaneanu L 《Endocrine pathology》1997,8(2):91-108
20.
Dini Ramadhani Takehiro Tsukada Ken Fujiwara Kotaro Horiguchi Motoshi Kikuchi Takashi Yashiro 《ACTA HISTOCHEMICA ET CYTOCHEMICA》2012,45(5):309-315
Laminin is a key component of the basement membrane and is involved in the structural scaffold and in cell proliferation and differentiation. Research has identified 19 laminin isoforms, which are assemblies of α, β, and γ chains (eg, the α1, β1, and γ1 chains form the laminin 111 isoform). Although laminin is known to be present in the anterior pituitary, the specific laminin isoforms have not been identified. This study used molecular biological and histochemical techniques—namely, RT-PCR, immunohistochemistry, and in situ hybridization—to identify the laminin isoforms and laminin-producing cells in rat anterior pituitary. RT-PCR showed that laminin α1, α3, and α4 genes were expressed in anterior pituitary. Immunohistochemistry revealed laminin α1 in gonadotrophs and laminin α4 in almost all vascular endothelial cells. Laminin α3 was seen in a subset of vascular endothelial cells. We then performed in situ hybridization to localize β and γ chains in these cells and found that laminin β1, β2, and γ1 were expressed in gonadotrophs and that laminin β1 and γ1 were expressed in endothelial cells. In conclusion, we identified gonadotroph-type (laminin 111 and 121) and vascular-type (laminin 411 and 311) laminin isoforms in rat anterior pituitary. 相似文献