Expression of Adrenocorticotropic Hormone, Prolactin and Transcriptional Factors in Clinically Nonfunctioning Pituitary Adenoma

Kageyama, Kazunori; Ikeda, Hidetoshi; Nigawara, Takeshi; Sakihara, Satoru; Suda, Toshio

doi:10.1507/endocrj.k07e-030

Cited by 11 publications

(7 citation statements)

References 24 publications

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“…Some SCAs are Tpit positive [25, 32] and express NeuroD1 [32–34], similar to observations in functional corticotroph adenomas. However, SCAs exhibit clinical behavior similar to aggressive nonfunctioning adenomas.…”

Section: Introductionsupporting

confidence: 65%

“…However, examination of Tpit in SCAs have yielded conflicting reports with one study showing Tpit positive immunohistochemistry staining in three of four SCAs [25] while another demonstrated lower Tpit mRNA levels in SCAs than in functional corticotroph adenomas [33]. NeuroD1, a factor contributing to differentiation of corticotroph adenomas and α-GSU positive cells, was also expressed in SCAs [32–34]. In addition to corticotroph markers and consistent with our findings here, a single SCA showed expression of gonadotroph markers, namely DAX-1 and SF-1 [34].…”

Section: Discussionmentioning

confidence: 99%

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Silent Corticogonadotroph Adenomas: Clinical and Cellular Characteristics and Long-Term Outcomes

et al. 2010

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Silent corticotrophins adenomas (SCAs) are clinically silent and non-secreting but immunostain positively for ACTH. We hypothesize that SCAs comprise both corticotroph and gonadotroph characteristics. Cohort analysis from 1994-2008 with follow-up time ranging from 1-15 years in a tertiary referral center. We compared preoperative and postoperative clinical results and tumor cytogenesis in 25 SCAs and 84 nonfunctioning adenomas in 109 consecutive patients diagnosed pre-operatively with nonfunctioning pituitary adenomas. Clinical outcomes were radiologic and hormonal measures. Pathologic outcomes were expression of relevant pituitary hormones, tissuespecific transcription factors, and electron microscopy features. Preoperative SCA presentation was similar to that observed for nonfunctioning adenomas. However, SCAs recurred postoperatively at a median of 3 years vs. 8 years for nonfunctioning adenomas (p<0.0001). Fiftyfour percent of patients with SCAs had new onset postoperative hypopituitarism vs. 17% of nonfunctioning adenomas (p<0.025). SCAs (n=18) were immunopositive for ACTH, cytoplasmic and nuclear SF-1, NeuroD1, DAX-1, and alpha-gonadotropin subunit, but Tpit negative, and coexpression of tumor ACTH with either SF-1 or LH was detected. In contrast, functional corticotroph adenomas (n=11) were immunopositive for ACTH, nuclear SF-1, NeuroD1, and Tpit, but negative for DAX-1, a gonadotroph cell transcription factor. Gonadotroph adenomas (n=23) were immunonegative for ACTH and Tpit but positive for nuclear SF-1, NeuroD1, and DAX-1. SCA electron microscopy demonstrated ultrastructural features consistent with corticotroph and

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Section: Introductionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Silent Corticogonadotroph Adenomas: Clinical and Cellular Characteristics and Long-Term Outcomes

et al. 2010

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“…Moreover, the typification of these tumors has been based on the IHC study of pituitary-specific hormones [28][29][30][31][32]. Only Kageyama et al [33] have described the IHC co-expression of NEUROD1, Tpit, and Pit-1 in a silent PitNET with positivity for ACTH and PRL. Our results suggest that this tumor subtype is more prevalent than initially thought.…”

Section: Discussionmentioning

confidence: 99%

How Valuable Is the RT-qPCR of Pituitary-Specific Transcription Factors for Identifying Pituitary Neuroendocrine Tumor Subtypes According to the New WHO 2017 Criteria?

Quesada

García‐Martínez

Silva-Ortega

et al. 2019

Cancers

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The classification of pituitary neuroendocrine tumors (PitNETs) subtypes continues generating interest. In 2017, the World Health Organization (WHO) proposed considering the immunohistochemical (IHC) analysis of pituitary-specific transcription factors (TF) for their typification. The present study targeted the quantification of pituitary-specific TF (TPIT, PIT-1, SF-1, GATA2, ESR1) gene expression by RT-qPCR to overcome the shortcomings of IHC and to complement it. We analyzed 251 tumors from our collection of PitNETs and performed additional IHC studies in a subset of 56 samples to analyze the concordance between gene and protein expression of the TF. The molecular and IHC studies allowed us to significantly reduce the percentage of null cell tumors in our series, most of which were reclassified as gonadotroph tumors. The concordance between the molecular and the immunohistochemical studies was good for tumors coming from the corticotroph and Pit-1 lineages but worsened for the rest of the tumors. Indeed, the RT-qPCR helped to improve the typification of plurihormonal Pit-1 and unusual tumors. Overall, our results suggest that the RT-qPCR of pituitary-specific TF and hormone genes could help pathologists, endocrinologists, and neurosurgeons to improve the management of patients with pituitary tumors.

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“…The criteria for rare (0.9%) silent poorly differentiated PIT1-positive tumors [14], previously known as silent type 3 adenomas [48], are still poorly defined. Silent tumors with other combinations of pituitary hormone expression such as GH-ACTH or PRL-ACTH or ACTH-LH are exceptional [49,50].…”

Section: Plurihormonal Tumorsmentioning

confidence: 99%

How to Classify Pituitary Neuroendocrine Tumors (PitNET)s in 2020

Trouillas

Jaffrain-Rea

Vasiljevic

et al. 2020

Cancers

139

104

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Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive, “aggressive” and malignant with metastases. They are classified into seven morphofunctional types and three lineages: lactotroph, somatotroph and thyrotroph (PIT1 lineage), corticotroph (TPIT lineage) or gonadotroph (SF1 lineage), null cell or immunonegative tumor and plurihormonal tumors. The WHO 2017 classification suggested that subtypes, such as male lactotroph, silent corticotroph and Crooke cell, sparsely granulated somatotroph, and silent plurihormonal PIT1 positive tumors, should be considered as “high risk” tumors. However, the prognostic impact of these subtypes and of each morphologic type remains controversial. In contrast, the French five-tiered classification, taking into account the invasion, the immuno-histochemical (IHC) type, and the proliferative markers (Ki-67 index, mitotic count, p53 positivity), has a prognostic value validated by statistical analysis in 4 independent cohorts. A standardized report for the diagnosis of pituitary tumors, integrating all these parameters, has been proposed by the European Pituitary Pathology Group (EPPG). In 2020, the pituitary pathologist must be considered as a member of the multidisciplinary pituitary team. The pathological diagnosis may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.

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Expression of Adrenocorticotropic Hormone, Prolactin and Transcriptional Factors in Clinically Nonfunctioning Pituitary Adenoma

Cited by 11 publications

References 24 publications

Silent Corticogonadotroph Adenomas: Clinical and Cellular Characteristics and Long-Term Outcomes

Silent Corticogonadotroph Adenomas: Clinical and Cellular Characteristics and Long-Term Outcomes

How Valuable Is the RT-qPCR of Pituitary-Specific Transcription Factors for Identifying Pituitary Neuroendocrine Tumor Subtypes According to the New WHO 2017 Criteria?

How to Classify Pituitary Neuroendocrine Tumors (PitNET)s in 2020

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