A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas.

2002 ◽  
pp. 103-113 ◽  
Author(s):  
M L Jaffrain-Rea ◽  
D Di Stefano ◽  
G Minniti ◽  
V Esposito ◽  
A Bultrini ◽  
...  
Keyword(s):  
Operative Treatment ◽  
Hormone Secretion ◽  
Tumour Volume ◽  
Pituitary Tumour ◽  
Labelling Index ◽  
Pituitary Tumours ◽  
Life Threatening ◽  
The Mean ◽  
Monoclonal Antibody Mib 1 ◽  
Mib 1

Pituitary tumours are usually benign neoplasia, but may have a locally aggressive or malignant evolution. This study aimed to identify factors which mostly influence their proliferative activity, in order to clarify its value for clinical and research purposes. The proliferative index was determined in a prospective series of 132 pituitary tumours as the percentage of monoclonal antibody MIB-1-immunopositive cells and referred to as the MIB-1 labelling index (LI). Its distribution was analysed according to both univariate and multivariate models. A life-threatening pituitary tumour is presented separately. The mean LI was 1.24+/-1.59%, with significant differences between clinically secreting (CS) and clinically non-secreting (CNS) adenomas. In CS adenomas (n=65), LI was highly variable and markedly influenced by pre-operative pharmacological treatment (0.80+/-1.03 vs 2.06+/-2.39% in treated vs untreated cases, P=0.009); it decreased with patient's age (P=0.025, r=0.28) and increased with tumour volume and invasiveness. The influence of pre-operative treatment and macroscopic features on LI in this group was confirmed by multivariate analysis. In CNS adenomas (n=67), LI distribution was less variable than in CS adenomas (P<0.0001), it was age-independent and correlations with tumour volume, invasiveness or recurrence did not reach significance. In a rapidly growing parasellar tumour, the mean LI was 24% at first surgery and exceeded 50% at second surgery performed 4 months later. LI should be interpreted according to hormone secretion and pre-operative treatment. Unusually high LI values deserve particular attention.

scholarly journals Medulloblastoma: evaluation of proliferative index by monoclonal antibody Mib-1, its prognostic correlation and therapeutic implications

2003 ◽  
Vol 61 (3A) ◽  
pp. 547-551 ◽  
Author(s):  
Antonio Fernandes Ferrari ◽  
Maria Betânia Mahler Araújo ◽  
Paulo Henrique Aguiar ◽  
José Pindaro Pereira Plese
Keyword(s):  
Monoclonal Antibody ◽  
Prognostic Value ◽  
Cellular Proliferation ◽  
Proliferation Index ◽  
Histopathological Diagnosis ◽  
Central Nervous System Tumor ◽  
Proliferative Index ◽  
The Mean ◽  
Monoclonal Antibody Mib 1 ◽  
Mib 1

In the past few years, the monoclonal antibody MIB-1 has been used by researchers in order to retrospectively study paraffin imbibed tumor fragments. The medulloblastoma is the most common malignant central nervous system tumor in childhood. The objectives were: determination of the mean Mib-1 LI value from these patients, as well as the prognostic value of the method.This retrospective study represents an analysis of the cellular proliferation index of posterior fossa medulloblastomas collected from 22 patients at A.C. Camargo Hospital, from January 1990 to December 1999. The histopathological diagnosis was confirmed by H&E and proliferative index (LI) was achived with Mib-1 which detects proliferating cells during G1, G2, S and M phases.The results demostrated that the mean Mib-1 was 30,1%, and ranged from 5,2% to 62,0%.In conclusion, this method has prognostic value, has to be used as routine for patients harboring medulloblastomas and the ones who have PI greater than the mean value found in this study, should be treated aggressively.

scholarly journals Correlation of VEGF production with IL1α and IL6 secretion by human pituitary adenoma cells

2005 ◽  
Vol 152 (2) ◽  
pp. 293-300 ◽  
Author(s):  
S A Borg ◽  
K E Kerry ◽  
J A Royds ◽  
R D Battersby ◽  
T H Jones
Keyword(s):  
Pituitary Adenoma ◽  
Tumour Volume ◽  
Pituitary Tumour ◽  
Angiogenic Factor ◽  
Tumour Cell Line ◽  
Pituitary Tumours ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Invasive Status ◽  
Significant Addition

Objectives: Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor involved in the neovascularisation of solid tumours. Regulatory molecules include cytokines and growth factors. Interleukin (IL)1 and IL6 have both been shown to regulate VEGF levels in a variety of tissues. The role of cytokines in the pathogenesis of pituitary tumours remains unclear. We have examined the expression of VEGF and its relationships with IL1 and IL6 in the human pituitary tumour cell line HP75 and a series of human pituitary tumours. We have also looked at the relationship of tumour volume and invasive status to VEGF secretion. Methods: Surgically resected tumours were routinely cultured in single-cell suspension at 200 K/well (standard unit for culture of dispersed primary pituitary adenoma cells). We measured VEGF, IL1α and IL6 levels by ELISA. Tumour volume and invasion grade were assessed by preoperative magnetic resonance imaging. Results: VEGF was detected in conditioned medium of HP75 cells (900±52 pg/ml) and in 82% of tumours tested (range 26–16 464 pg/ml). Tumour volume and secretion of VEGF were significantly associated with levels of IL6 (volume, P = 0.056; VEGF, P < 0.001 (P values based on Spearman’s test)) and IL1α produced (volume, P < 0.005; VEGF, P < 0.001). Invasive tumours showed a higher basal secretion of VEGF that that of the non-invasive type; however, this difference was not significant. Addition of exogenous IL1α, but not IL6, significantly increased VEGF production. Conclusions: The significant associations between VEGF and the levels of IL6 and IL1α suggest an important role for these cytokines in the development of these tumours.

Effects of bromocriptine-induced pregnancy on prolactin-secreting pituitary tumours

1981 ◽  
Vol 98 (3) ◽  
pp. 333-338 ◽  
Author(s):  
T. Bergh ◽  
S. J. Nillius ◽  
S.-G. Larsson ◽  
L. Wide
Keyword(s):  
Post Partum ◽  
Pituitary Tumour ◽  
X Rays ◽  
Pituitary Tumours ◽  
Pituitary Fossa ◽  
X Ray ◽  
Pregnancy And Lactation ◽  
Radiological Changes ◽  
The Mean

Abstract. Twenty-eight women with hyperprolactinaemia and amenorrhoea received bromocriptine treatment which resulted in 31 term pregnancies. Bromocriptine treatment was stopped as soon as pregnancy was established. Nineteen of the women had radiological signs of a pituitary tumour. The pregnancies were clinically un-eventful in all cases except one who developed headache. Post-partum sellar X-ray showed pregnancy-induced enlargement of the pituitary fossa in 4 of the 28 women. Regression of the radiological changes occurred in 3 of the 4 women within 2 years after the delivery. The women with abnormal sellar X-rays had no difference in the mean prolactin levels before treatment and after pregnancy and lactation while all the women with normal sellae had lower prolactin levels after pregnancy than before. Three women resumed regular spontaneous menstruations after pregnancy and lactation but only one conceived again. Thus, serious pituitary tumour complications are rare in hyperprolactinaemic women with bromocriptine-induced pregnancies. The pregnancy does not worsen the condition. Resolution of hyperprolactinaemia after bromocriptine-induced pregnancy is an unfrequent finding.

scholarly journals Temozolomide treatment of a pituitary carcinoma and two pituitary macroadenomas resistant to conventional therapy

2009 ◽  
Vol 161 (4) ◽  
pp. 631-637 ◽  
Author(s):  
C Hagen ◽  
H D Schroeder ◽  
S Hansen ◽  
C Hagen ◽  
M Andersen
Keyword(s):  
Dna Methyltransferase ◽  
English Literature ◽  
Tumour Size ◽  
Tumour Volume ◽  
Pituitary Tumour ◽  
Tumour Mass ◽  
Pituitary Tumours ◽  
Hormone Levels ◽  
Mass Effects ◽  
Methylguanine Dna Methyltransferase

ObjectiveAggressive pituitary tumours may be difficult to treat. Temozolomide (TMZ) is an alkylating cytostaticum. In a small number of cases, TMZ therapy has been reported to reduce pituitary tumour size and hormone hypersecretion.DesignWe present three patients with pituitary tumours treated with TMZ. One tumour was initially a macroprolactinoma that developed into a mixed GH- and prolactin-secreting carcinoma (patient A). To our knowledge, this is the first published in English literature. Two adenomas, a macroprolactinoma (patient B) and a clinically non-functioning pituitary adenoma (patient C), were highly invasive. The three patients suffered from extensive tumour mass effects, and all tumours were resistant to conventional treatment.MethodTMZ, 150–200 mg/m2 of body surface area was administered orally for 5 days during each 28-day cycle.ResultDuring TMZ therapy, tumour sizes were significantly reduced, hormone levels normalized and symptoms of mass effects decreased in all three cases. The carcinoma was treated from 2004 to 2006 (23 months). Three years after the terminating treatment, the tumour has not regrown and hormone levels are normalized. Immunohistochemical staining for methylguanine DNA methyltransferase (MGMT) was negative in two patients (A and B), and in one patient (C) a few nuclei stained positive.ConclusionTMZ therapy significantly decreased tumour volume, hormone hypersecretion and symptoms in all three patients, corresponding to the pathological findings regarding MGMT. TMZ therapy may be a new option for the treatment of resistant pituitary adenomas.

scholarly journals Natriuretic Peptide Expression and Function in GH3 Somatolactotropes and Feline Somatotrope Pituitary Tumours

2021 ◽  
Vol 22 (3) ◽  
pp. 1076
Author(s):  
Samantha M. Mirczuk ◽  
Christopher J. Scudder ◽  
Jordan E. Read ◽  
Victoria J. Crossley ◽  
Jacob T. Regan ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Tumour Volume ◽  
Pituitary Tumour ◽  
Gh3 Cells ◽  
Loss Of Function ◽  
Pituitary Tumours ◽  
Human Pituitary ◽  
Oestrogen Treatment ◽  
And Function

Patients harbouring mutations in genes encoding C-type natriuretic peptide (CNP; NPPC) or its receptor guanylyl cyclase B (GC-B, NPR2) suffer from severe growth phenotypes; loss-of-function mutations cause achondroplasia, whereas gain-of-function mutations cause skeletal overgrowth. Although most of the effects of CNP/GC-B on growth are mediated directly on bone, evidence suggests the natriuretic peptides may also affect anterior pituitary control of growth. Our previous studies described the expression of NPPC and NPR2 in a range of human pituitary tumours, normal human pituitary, and normal fetal human pituitary. However, the natriuretic peptide system in somatotropes has not been extensively explored. Here, we examine the expression and function of the CNP/GC-B system in rat GH3 somatolactotrope cell line and pituitary tumours from a cohort of feline hypersomatotropism (HST; acromegaly) patients. Using multiplex RT-qPCR, all three natriuretic peptides and their receptors were detected in GH3 cells. The expression of Nppc was significantly enhanced following treatment with either 100 nM TRH or 10 µM forskolin, yet only Npr1 expression was sensitive to forskolin stimulation; the effects of forskolin and TRH on Nppc expression were PKA- and MAPK-dependent, respectively. CNP stimulation of GH3 somatolactotropes significantly inhibited Esr1, Insr and Lepr expression, but dramatically enhanced cFos expression at the same time point. Oestrogen treatment significantly enhanced expression of Nppa, Nppc, Npr1, and Npr2 in GH3 somatolactotropes, but inhibited CNP-stimulated cGMP accumulation. Finally, transcripts for all three natriuretic peptides and receptors were expressed in feline pituitary tumours from patients with HST. NPPC expression was negatively correlated with pituitary tumour volume and SSTR5 expression, but positively correlated with D2R and GHR expression. Collectively, these data provide mechanisms that control expression and function of CNP in somatolactotrope cells, and identify putative transcriptional targets for CNP action in somatotropes.

scholarly journals The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas

2003 ◽  
pp. 203-211 ◽  
Author(s):  
JA Hunter ◽  
RH Skelly ◽  
SJ Aylwin ◽  
JF Geddes ◽  
J Evanson ◽  
...  
Keyword(s):  
Tumour Volume ◽  
Pituitary Tumour ◽  
Pituitary Hormones ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Pituitary Tumours ◽  
Gh Secretion ◽  
Endothelial Growth Factor ◽  
Transforming Gene

OBJECTIVE: Pituitary tumour transforming gene (PTTG) is a recently identified protooncogene, ubiquitously expressed in pituitary tumours at levels higher than those detected in normal pituitary. Although the precise function of PTTG protein is unknown, in vitro experiments have shown that it induces angiogenesis. In this study, we have examined the potential relationship between the level of PTTG expression and tumour phenotype, tumour size, in vitro pituitary hormone secretion and release of vascular endothelial growth factor (VEGF), a potent angiogenic factor. METHODS: Pituitary tumours (12 somatotroph, five lactotroph, five corticotroph and 18 non-functioning) were studied by cell culture, measuring the basal secretion of anterior pituitary hormones and VEGF in vitro. Immunocytochemistry was used to confirm the clinical diagnosis and tumour phenotype. PTTG mRNA expression was investigated by comparative RT-PCR. Tumour Volume was quantitated from pre-operative MRI scans. RESULTS: PTTG expression was significantly increased 2.7-fold in somatotroph tumours compared with non-functioning adenomas (P<0.01, ANOVA). A positive correlation was demonstrated between PTTG expression and in vitro GH secretion (r=0.41, P<0.01, Spearman) but no correlations were found for any of the other pituitary hormones. In 16 out of 40 pituitary tumours, we were able to determine the in vitro secretion of VEGF and relate this to PTTG expression. All of the adenomas tested secreted measurable VEGF but there was no correlation between the amount of VEGF secreted and either the tumour phenotype or PTTG expression. Neither PTTG expression nor VEGF secretion correlated with tumour Volume. CONCLUSIONS: Our studies have confirmed the presence of PTTG in pituitary adenomas and demonstrated a higher level of expression in somatotroph tumours and a significant correlation with GH secretion. We failed to demonstrate a relationship between PTTG expression and production of the angiogenic factor, VEGF, or tumour Volume. Thus, although PTTG induces angiogenesis experimentally, it seems unlikely that a VEGF-mediated angiogenic mechanism occurs during pituitary tumour progression.

HYPERPROLACTINAEMIA IN AMENORRHOEA - INCIDENCE AND CLINICAL SIGNIFICANCE

1977 ◽  
Vol 86 (4) ◽  
pp. 683-694 ◽  
Author(s):  
Torbjörn Bergh ◽  
Sven Johan Nillius ◽  
Leif Wide
Keyword(s):  
Pituitary Tumour ◽  
Follicular Phase ◽  
Control Group ◽  
Pituitary Hormone ◽  
X Rays ◽  
Pituitary Tumours ◽  
Early Follicular Phase ◽  
The Mean ◽  
Lh Rh ◽  
Rule Out

ABSTRACT Prolactin concentrations in serum were determined in 287 women with amenorrhoea. The incidence of hyperprolactinaemia was 14.6 per cent. All but 4 of the 31 women with persistent hyperprolactinaemia had galactorrhoea. Radiological signs suggestive of a pituitary tumour were seen in 48 per cent of the hyperprolactinaemic women, while only 4.5 per cent of the 245 normoprolactinaemic women had abnormal sellar X-rays. All the patients with prolactin concentrations above 100 μg/I had radio-logically abnormal sellae, but lower prolactin levels did not rule out the existence of even large pituitary tumours. The hyperprolactinaemic women with normal and abnormal sellae and a control group of healthy women in the early follicular phase all had similar mean basal FSH and LH levels with one exception, the group with abnormal sellae had lower basal LH levels than the control group. There was no difference in the mean FSH and LH responses to LH-RH between the hyperprolactinaemic women with pathological sellae and the control group while the hyperprolactinaemic women with normal sellae had higher responses than the other two groups. Prolactin determinations were found to be superior to other pituitary hormone estimations for identifying patients who are at risk of having pituitary tumours.

Molecular pathogenesis of pituitary tumours

2011 ◽  
pp. 112-121
Author(s):  
Ines Donangelo ◽  
Shlomo Melmed
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenomas ◽  
Single Cells ◽  
Hormone Secretion ◽  
Cell Types ◽  
Pituitary Tumour ◽  
Thyroid Stimulating Hormone ◽  
Gene Products ◽  
Pituitary Tumours ◽  
Secretory Products

Pituitary adenomas are discovered in up to 25% of unselected autopsies, however, clinically apparent tumours are considerably less common. The pituitary gland is composed of differentiated cell types: somatotrophs, lactotrophs, corticotrophs, thyrotrophs, and gonadotrophs. Tumours may arise from any of these cell types and their secretory products depend on the cell of origin. The functional classification of pituitary tumorus is based on identification of cell gene products by immunostaining or mRNA detection, as well as measurement of circulating tumour and target organ hormone levels. Oversecretion of adrenocorticotropic hormone (ACTH) results in cortisol excess with Cushing’s disease. Growth hormone overproduction leads to acromegaly with typical acral overgrowth and metabolic abnormalities. Prolactin hypersecretion results in hypogonadism and galactorrhoea. Rarely, thyroid-stimulating hormone (TSH) hypersecretion leads to goitre and thyrotoxicosis, and gonadotropin excess results in gonadal dysfunction (1). Mixed tumours cosecreting growth hormone with prolactin, TSH, or ACTH may also arise from single cells. Clinically nonfunctional tumours are those that do not efficiently secrete their gene products, and most commonly they are derived from gonadotroph cells. Pituitary tumours are further defined radiographically as microadenomas (<1 cm in diameter) or macroadenomas (>1 cm in diameter). However, this classification does not reflect whether the pituitary tumour is amenable to total resection and limits assessment of invasive progression during serial imaging. Therefore, it is useful to apply the classification proposed by Hardy in 1973 and modified by Wilson in 1990 (Table 2.3.2.1), whereby pituitary tumours are classified into one of five grades and one of six stages, providing important preoperative information. Pituitary tumours cause morbidity by both abnormal hormone secretion as well as compression of regional structures. As a considerable proportion of patients do not achieve optimal therapeutic control of mass effects and/or hormone hypersecretion despite advances in therapeutic approaches, understanding pathogenesis and pituitary tumour growth patterns in individual patients will enable identification of subcellular treatment targets, ultimately decreasing tumour-related morbidity and mortality. Determinants of initiation and progression of pituitary adenomas are not fully understood. This chapter describes a spectrum of mechanisms implicated in pituitary tumorigenesis, including the role of pituitary plasticity, imbalances in cell cycle regulation, transcription factors, signalling pathways, and angiogenesis (Fig. 2.3.2.1). Molecular events related to tumorigenesis in human pituitary adenoma subtypes are summarized in Table 2.3.2.2. The causal role for selected genetic imbalances leading to development of pituitary tumours has been confirmed in several transgenic mouse models (Table 2.3.2.3).

scholarly journals Massive haemorrhagic complications of ruptured pulmonary arteriovenous malformations: outcomes from a 12 years’ retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xu Ma ◽  
Bing Jie ◽  
Dong Yu ◽  
Ling-Ling Li ◽  
Sen Jiang
Keyword(s):  
Arteriovenous Malformations ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Pulmonary Arteriovenous Malformations ◽  
Imaging Data ◽  
Peripheral Lung ◽  
Life Threatening ◽  
The Mean

Abstract Background The life-threatening haemorrhagic complications of pulmonary arteriovenous malformations (PAVMs) are extremely rare, and only described in isolated cases. This study was designed to comprehensively investigate management of ruptured PAVMs. Methods We retrospectively assessed clinical and imaging data of ruptured PAVMs to summarize incidence, clinical characteristics, and outcomes following embolisation between January 2008 and January 2021. Results Eighteen of 406 (4.4%) patients with PAVMs developed haemorrhagic complications. Twelve of 18 patients were clinically diagnosed with hereditary haemorrhagic telangiectasia (HHT). Haemorrhagic complications occurred with no clear trigger in all cases. Eight of 18 patients (44.4%) were initially misdiagnosed or had undergone early ineffective treatment. 28 lesions were detected, with 89.3% of them located in peripheral lung. Computed tomography angiography (CTA) showed indirect signs to indicate ruptured PAVMs in all cases. Lower haemoglobin concentrations were associated with the diameter of afferent arteries in the ruptured lesions. Successful embolotherapy was achieved in all cases. After embolotherapy, arterial oxygen saturation improved and bleeding was controlled (P < 0.05). The mean follow-up time was 3.2 ± 2.5 years (range, 7 months to 10 years). Conclusions Life threatening haemorrhagic complications of PAVMs are rare, they usually occur without a trigger and can be easily misdiagnosed. HHT and larger size of afferent arteries are major risk factors of these complications. CTA is a useful tool for diagnosis and therapeutic guidance for ruptured PAVMs. Embolotherapy is an effective therapy for this life-threatening complication.

scholarly journals Effect of COVID-19 outbreak on emergency department attendances in an Italian academic hospital

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
M Poletto ◽  
G Perri ◽  
F Malacarne ◽  
B Bianchet ◽  
A Doimo ◽  
...  
Keyword(s):  
Emergency Department ◽  
Initial Phase ◽  
Mainland China ◽  
Hospital Setting ◽  
Academic Hospital ◽  
Significant Difference ◽  
Before And After ◽  
Life Threatening ◽  
The Mean ◽  
Critical Patients

Abstract Background Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was discovered during the 2019 outbreak in Mainland China and the first cases were reported in Italy on February 21, 2020. This study evaluates the emergency department (ED) attendances of an academic hospital in northern Italy before and after media reported the news of the first infected patients in Italy. Methods Adult attendances in ED in February 2020 were analysed dividing the period into 4 weeks (days 1-7, 8-14, 15-21, 22-28) compared with the same periods in 2019. The visits were analysed separately according to the Italian colour code of triage: white (non-critical), green (low-critical), yellow (medium critical), red (life-threatening). The mean weekly number of attendances was compared with t-test. Results February 2020 total ED attendances compared with February 2019 were 4865 vs 5029 (-3.3%), of which white codes were 834 vs 762 (+9.4%), green 2450 vs 2580 (-5.0%), yellow 1427 vs 1536 (-7.1%), red 154 vs 151 (+2.0%). February 2020 weekly mean ED attendances compared with February 2019 had statistically significant difference only in the fourth week (days 22-28) for green codes (75 vs 92, p = 0.007) and yellow codes (41 vs 52, p = 0.047), not for white (27 vs 26, p = 0.760) and red codes (5 vs 5, p = 0.817). The first three weeks of February 2020 compared with 2019 showed no statistically significant difference in weekly mean ED attendances. Conclusions There was a significant reduction of green and yellow codes attendances at ED in the fourth week of February 2020, corresponding to the initial phase of Italian COVID-19 outbreak. The fear of contracting SARS-CoV-2 by attending the ED probably acted as a significant deterrent in visits, especially for low and medium critical patients. Additional data are required to better understand the phenomenon, including the behaviour of non-critical attendances. Key messages A reduction of green and yellow codes attendances was reported during initial phase of COVID-19 outbreak in an Italian academic hospital. Fear of contracting COVID-19 infection in a hospital setting could impact on emergency department attendances.

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