KIT protein expression and mutational status of KIT gene in pituitary adenomas

Casar‐Borota, Olivera; Fougner, Stine Lyngvi; Bollerslev, Jens; Nesland, Jahn M.

doi:10.1007/s00428-011-1185-8

Cited by 11 publications

(6 citation statements)

References 41 publications

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“…Unlike their study, we found predominant expression of c-kit in NFPA and somatotropinomas, though we have not examined any patient with corticotropinoma and the intensity of positivity varied from tumor subtypes. Similar to our study, Casar et al found cytoplasmic c-kit positivity in 52.4% and membranous positivity in 8.3% (9). Usually it is believed that the mutated protein translocates into the nucleus and gives nuclear positivity.…”

Section: Discussionsupporting

confidence: 92%

Imatinib Inhibits GH Secretion From Somatotropinomas

et al. 2018

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Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line.Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/β) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways.Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-β (PDGFR-β; P < 0.009 and P < 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01) and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-β pathway.Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas.

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Section: Discussionsupporting

confidence: 92%

Imatinib Inhibits GH Secretion From Somatotropinomas

et al. 2018

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“…Patients with Nelson’s syndrome were included in the previously established cohort, while only adult patients with corticotroph functioning PitNETs were used for the present comparison. Moreover, only limited clinical data (gender, age, tumour size (micro/macro)) were available for the corticotroph functioning PitNETs [ 23 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

“…The original haematoxylin eosin stained sections from all tumours were reviewed to confirm the presence of pituitary tumour tissue. TMAs were constructed containing replicate 1 mm cores from formalin-fixed paraffin embedded tissue samples from representative areas [ 29 , 30 ].…”

Section: Methodsmentioning

confidence: 99%

Distribution of E- and N-cadherin in subgroups of non-functioning pituitary neuroendocrine tumours

et al. 2022

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Purpose Clinically non-functioning pituitary neuroendocrine tumours (NF-PitNETs) present a varying degree of aggressiveness, and reliable prognostic markers are lacking. We aimed to characterise the distribution of E- and N-cadherin in corticotroph, PIT1 and null-cell NF-PitNETs, and link it to the course of the tumours. Methods The distribution of E- and N-cadherin was investigated by immunohistochemistry in a retrospective cohort of 30 tumours of the less common NF-PitNETs (corticotroph (N = 18), PIT1 (N = 8) and null-cell PitNETs (N = 4)). Immunoreactive scores (IRS) were compared to previously presented cohorts of gonadotroph NF-PitNETs (N = 105) and corticotroph functioning PitNETs (N = 17). Results We found a low IRS for the extra-cellular domain of E-cadherin (median 0 (IQR 0–0, N = 135)), a medium to high IRS for the intra-cellular domain of E-cadherin (median 6 (IQR 4–9)) and a high IRS for N-cadherin (median 12 (IQR 10.5–12)) throughout the cohort of NF-PitNETs. The corticotroph NF-PitNETs presented a higher IRS for both the extra- and intra-cellular domain of E-cadherin (median 0 (IQR 0–1) and median 9 (IQR 6–12), respectively) than the gonadotroph NF-PitNETs (p < 0.001 for both comparisons). Presence of nuclear E-cadherin was associated with a weaker staining for the intra-cellular domain of E-cadherin (median 4 (IQR 0.5–6) and median 9 (IQR 9–12), for tumours with and without nuclear E-cadherin, respectively), and with a lower rate of re-intervention (p = 0.03). Conclusions Considering our results and the benign course of NF-PitNETs, we suggest that a high N-cadherin and downregulation of membranous E-cadherin are not associated with a more aggressive tumour behaviour in these subgroups of NF-PitNETs.

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“…35 However, it is worth noting that CD117 expression, not associated with c-kit mutation, has also been documented in a subgroup of ACTH pituitary adenomas. 36,37 The meaning of CD117 expression in corticotrophs is not clear, nor is its expression in PanNETs. The monoclonal antibody 331.3, recognizing the COOH-terminal portion of both BCL10 and carboxyl ester lipase, is useful to identify pancreatic acinar cells and ACCs.…”

Section: Acth-secreting Accmentioning

confidence: 99%

ACTH-secreting Pancreatic Neoplasms Associated With Cushing Syndrome

Maragliano

Vanoli

Albarello

et al. 2015

American Journal of Surgical Pathology

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Adrenocorticotropic hormone (ACTH)-secreting pancreatic neuroendocrine tumors (PanNETs), although rare, are responsible for about 15% of ectopic Cushing syndrome (CS). They represent a challenging entity because their preoperatory diagnosis is frequently difficult, and clear-cut morphologic criteria useful to differentiate them from other types of PanNETs have not been defined. Ectopic ACTH secretion associated with CS can also be rarely due to pancreatic acinar cell carcinoma (ACC) and pancreatoblastoma, rare tumor types with morphologic features sometimes overlapping those of PanNETs and, for this reason, representing a diagnostic challenge for pathologists. We herein describe the clinicopathologic and immunohistochemical features of 10 PanNETs and 1 ACC secreting ACTH and associated with CS together with an extensive review of the literature to give the reader a comprehensive overview on ACTH-producing pancreatic neoplasms. ACTH-secreting PanNETs are aggressive neoplasms with an immunohistochemical profile that partially overlaps that of pituitary corticotroph adenomas. They are generally large and well-differentiated neoplasms without distinctive histologic features but with signs of aggressiveness including vascular and perineural invasion. They are more frequent in female individuals with a mean age of 42 years. At 5 and 10 years after diagnosis, 35% and 16.2% of patients, respectively, were alive. ACTH-secreting ACCs and pancreatoblastomas are very aggressive pediatric tumors with a poor prognosis. Using an appropriate immunohistochemical panel including ACTH, β-endorphin, trypsin, and BCL10 it is possible to recognize ACTH-secreting PanNETs and to distinguish them from the very aggressive ACTH-secreting ACCs.

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KIT protein expression and mutational status of KIT gene in pituitary adenomas

Cited by 11 publications

References 41 publications

Imatinib Inhibits GH Secretion From Somatotropinomas

Imatinib Inhibits GH Secretion From Somatotropinomas

Distribution of E- and N-cadherin in subgroups of non-functioning pituitary neuroendocrine tumours

ACTH-secreting Pancreatic Neoplasms Associated With Cushing Syndrome

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