High-risk pituitary adenomas and strategies for predicting response to treatment

Kontogeorgos, George; Thodou, Eleni; Osamura, R. Yoshiyuki; Lloyd, Ricardo V.

doi:10.1007/s42000-021-00333-y

Cited by 15 publications

(20 citation statements)

References 117 publications

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“…This may affect the results of treating these patients with dopamine analogs like cabergoline. In general, the identified gene expression patterns correspond to literature data indicating that patients with sparsely granulated tumors are considered as high risk tumors (Kontogeorgos et al , 2022) as they have have worse prognosis, lower rate of postoperative remission, tumors with frequent invasive growth, a tendency to regrow after surgery and lower response to SRLs (Kontogeorgos et al , 2022). Our transcriptomic data indicate that these tumors may be significantly driven by ghrelin signaling.…”

Section: Discussionsupporting

confidence: 79%

“…Addidtionally it is caused by mixed somatotrophlactotroph tumors (composed of two distinct populations of somatotroph and lactotroph tumor cells), immature PIT-1-lineage tumors and acidophil stem cell tumors (Asa et al, 2022a). SG somatotroph PitNETs and plurihormonal PIT-1 positive PitNETs are categorized as high-risk tumors due to characteristics of aggressiveness including invasive growth and higher recurrence rate (Kontogeorgos et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomic classification of pituitary neuroendocrine tumors causing acromegaly

Rymuza

Kober

Rusetska

et al. 2022

Preprint

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Acromegaly results from growth hormone hypersecretion caused by somatotroph pituitary neuroendocrine tumor (PitNET). Our molecular profiling revealed that acromegaly-causing tumors form three distinct transcriptomic subgroups with different histological/clinical features. Transcriptomic subtypes of somatotroph tumors differ in the expression levels of numerous genes including those involved in hormone secretion and genes with known prognostic value. They can be distinguished by determining the expression of marker genes. Transcriptomic group 1 includes ~20% of acromegaly patients with GNAS mutations-negative, mainly densely granulated tumors with NR5A1 (SF-1) and GIPR co-expression. Group 2 tumors are the most common (46%) and include mainly GNAS-mutated, densely granulated somatotroph and mixed PitNETs. They have significantly smaller size and express favorable prognosis-related genes. Group 3 includes predominantly sparsely granulated somatotroph PitNETs with low GNAS mutations frequency causing ~35% of acromegaly cases. Ghrelin signaling is implied in their pathogenic mechanism, they have unfavorable gene expression profile, and invasive growth rate. Since a subgroup of somatotroph tumors have high NR5A1 expression, using SF-1 as classification marker specific to gonadotroph PitNETs could be reconsidered.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Transcriptomic classification of pituitary neuroendocrine tumors causing acromegaly

Rymuza

Kober

Rusetska

et al. 2022

Preprint

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“…In contrast to CD-causing adenomas which are commonly small microadenomas, SCAs are diagnosed as macroadenomas due to neurological symptoms related to tumor mass. They are characterized by invasive growth, high risk of recurrence and resistance to medical therapy and are therefore referred to as “high-risk” pituitary adenomas according to current classification [ 3 , 4 ]. In our study, the SCAs were larger than functioning counterparts, as expected.…”

Section: Discussionmentioning

confidence: 99%

“…Frequently they show invasive growth and increased proliferation index [ 1 ]. According to current recommendations, SCAs are now referred to as “high-risk” pituitary adenomas which refers to their fast and invasive growth, high risk of recurrence and resistance to medical therapy [ 3 , 4 ]. They are recognized to be more aggressive than other clinically nonfunctioning pituitary tumors such as those of gonadotroph origin or null-cell adenomas [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Difference in miRNA Expression in Functioning and Silent Corticotroph Pituitary Adenomas Indicates the Role of miRNA in the Regulation of Corticosteroid Receptors

Mossakowska

Kober

Rusetska

et al. 2022

IJMS

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Corticotroph pituitary adenomas commonly cause Cushing’s disease (CD), but some of them are clinically silent. The reason why they do not cause endocrinological symptoms remains unclear. We used data from small RNA sequencing in adenomas causing CD (n = 28) and silent ones (n = 20) to explore the role of miRNA in hormone secretion and clinical status of the tumors. By comparing miRNA profiles, we identified 19 miRNAs differentially expressed in clinically functioning and silent corticotroph adenomas. The analysis of their putative target genes indicates a role of miRNAs in regulation of the corticosteroid receptors expression. Adenomas causing CD have higher expression of hsa-miR-124-3p and hsa-miR-135-5p and lower expression of their target genes NR3C1 and NR3C2. The role of hsa-miR-124-3p in the regulation of NR3C1 was further validated in vitro using AtT-20/D16v-F2 cells. The cells transfected with miR-124-3p mimics showed lower levels of glucocorticoid receptor expression than control cells while the interaction between miR-124-3p and NR3C1 3′ UTR was confirmed using luciferase reporter assay. The results indicate a relatively small difference in miRNA expression between clinically functioning and silent corticotroph pituitary adenomas. High expression of hsa-miR-124-3p in adenomas causing CD plays a role in the regulation of glucocorticoid receptor level and probably in reducing the effect of negative feedback mediated by corticosteroids.

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“…Thus, it is of great significance to identify high-risk adenoma types early and accurately. Kontogeorgos et al (32) recommended that in order to achieve precise histological classification, IHC for pituitary hormones and cytokeratins to identify high-risk adenoma types were required. Moreover, assessment of predictive markers by IHC played an important clinical role in pathology, contributing to achieving the maximum of the expected effectiveness of treatment.…”

Section: Literature Review and Discussionmentioning

confidence: 99%

A Pituitary Carcinoma Patient With Cerebrospinal Fluid Dissemination Showing a Good Response to Temozolomide Combined With Whole-Brain and Spinal Cord Radiotherapy: A Case Report and Literature Review

et al. 2022

Front. Oncol.

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Pituitary carcinoma (PC) is extremely rare, with its incidence only accounting for 0.1%-0.2% of pituitary tumor (PT). Existing histological features, including invasiveness, cellular pleomorphism, nuclear atypia, mitosis, necrosis, etc., can be observed in pituitary adenoma (PA), invasive PA (IPA) and PC. Invasion is not the basis for the diagnosis of PC. The diagnosis of PC is often determined after the metastases are found, hence early diagnosis is extraordinarily difficult. Owing to the conventional treatment for PC may not be effective, a large portion of patients survived less than one year after diagnosis. Therefore, it is of great significance to find an efficacious treatment for PC. We report a rare case of sparsely granulated somatotroph carcinoma with cerebrospinal fluid dissemination showing a favorable treatment response to temozolomide (TMZ) combined with whole-brain and spinal cord radiotherapy.

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High-risk pituitary adenomas and strategies for predicting response to treatment

Cited by 15 publications

References 117 publications

Transcriptomic classification of pituitary neuroendocrine tumors causing acromegaly

Transcriptomic classification of pituitary neuroendocrine tumors causing acromegaly

Difference in miRNA Expression in Functioning and Silent Corticotroph Pituitary Adenomas Indicates the Role of miRNA in the Regulation of Corticosteroid Receptors

A Pituitary Carcinoma Patient With Cerebrospinal Fluid Dissemination Showing a Good Response to Temozolomide Combined With Whole-Brain and Spinal Cord Radiotherapy: A Case Report and Literature Review

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