PTTG overexpression in non-functioning pituitary adenomas: Correlation with invasiveness, female gender and younger age

Trott, Geraldine; Ongaratti, Bárbara Roberta; Silva, Camila Batista de Oliveira; Abech, Gabriel Dotta; Haag, Taiana; Rech, Carolina Garcia Soares Leães; Ferreira, Nelson Pires; Oliveira, Miriam da Costa; Pereira-Lima, Júlia Fernanda Semmelmann

doi:10.1016/j.anndiagpath.2019.04.016

Cited by 19 publications

(22 citation statements)

References 60 publications

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“…PTTG1 is a growth factor with a well-established role in carcinogenesis and invasion, partly regulated through the c-myc pathway ( 224 ). A meta-analysis has confirmed increased PTTG1 expression in invasive pituitary tumors ( 225 ) (this has also been replicated in NFPTs ( 226 )). Pituitary tumors show a global increase in H3K9 acetylation compared to normal pituitary, with increased acetylation seen in tumors with increased Ki-67 index ( 227 ).…”

Section: Epigenetic Mechanisms Of Tumorigenesismentioning

confidence: 77%

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

Nadhamuni

Korbonits

2020

Endocrine Reviews

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Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or non-syndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and non-coding RNAs, such as microRNA, long noncoding RNAs and circular RNAs. These mechanisms can influence tumor formation, growth and invasion. While genetic and epigenetic mechanisms often disrupt similar pathways, such as cell cycle regulation, in pituitary tumors there is little overlap between genes altered by germline, somatic and epigenetic mechanisms. The interplay between these complex mechanisms driving tumorigenesis are best studied in the emerging multi-omics studies. Here, we summarize insights from the recent developments in the regulation of pituitary tumorigenesis.

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Section: Epigenetic Mechanisms Of Tumorigenesismentioning

confidence: 77%

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

Nadhamuni

Korbonits

2020

Endocrine Reviews

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“…This finding has been also observed in nongNFPA patients. In fact, women with nongNFPA, the preoperative duration of symptoms is shorter, the tumors are larger and more invasive, and the clinical outcome is worse than in men [13,14]. These findings are just the opposite of what have been described in gPRLoma [15,16].…”

Section: Discussionmentioning

confidence: 99%

Giant Non-Functioning Pituitary Adenoma: Clinical Characteristics and Therapeutic Outcomes

Iglesias

Arcano

Triviño

et al. 2020

Exp Clin Endocrinol Diabetes

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Background Giant pituitary adenoma (≥4 cm) is a rare tumor whose clinical features and prognosis are not well known. Aim To evaluate the clinical characteristics and therapeutic outcomes of giant non-functioning PA (gNFPA). Patients and Methods A retrospective multicenter study of gNFPA patients diagnosed in a 12-year period was performed. In each patient, clinical data and therapeutic outcomes were registered. Results Forty patients (24 men, age 54.2 ± 16.2 years) were studied. The maximum tumor diameter [median (interquartile range)] was 4.6 cm (4.1–5.1). Women had larger tumors [4.8 cm (4.2–5.4) vs. 4.5 cm (4.0–4.9); p=0.048]. Hypopituitarism [partial (n=22, 55%) or complete (n=9, 22.5%)] at diagnosis was present in 77.5% of the patients. Visual field defects were found in 90.9%. The most used surgical technique was endoscopic endonasal transsphenoidal (EET) surgery (n=31, 77.5%). Radiotherapy was used in 11 (27.5%) patients (median dose 50.4 Gy, range 50–54). Thirty-seven patients were followed for 36 months (10–67 months). Although more than half of these patients showed tumor persistence (n=25, 67.6%), tumor size was significantly reduced [0.8 cm (0–2.5); p<0.001]. At last visit, 12 patients (32.4%) showed absence of tumor on MRI. Hypopituitarism rate was similar (75.0%), although with significant changes (p<0.001) in the distribution of the type of hypopituitarism. The absence of tumor at the last visit was positively associated with positive immunohistochemical staining for FSH (p=0.01) and LH (p=0.006) and negatively with female sex (p=0.011), cavernous sinus invasion (p=0.005) and the presence of Knosp grade 4 (p=0.013). Conclusion gNFPAs are more frequent in men but tumors are larger in women. Surgical treatment is followed by a complete tumor resection rate of approximately 30%. Positive immunostaining for gonadotropins is associated with tumor absence at last revision, while female sex and invasion of the cavernous sinuses with tumor persistence.

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“…PTTG is also involved in angiogenesis via induction of FGF and VEGF [110]. Overexpression of PTTG contributes to cellular transformation and tumor development and has been implicated in endocrine and non-endocrine tumors, including those of the pituitary, thyroid, ovary, breast, prostate, lung, esophagus, colon, and central nervous system [110,111]. PTTG is overexpressed in approximately 90% of pituitary adenomas compared with low or no expression in normal pituitary tissue and PTTG has been demonstrated to correlate with Ki67 and tumor invasiveness and aggression [111][112][113].…”

Section: Pituitary Tumor-transforming Gene (Pttg)mentioning

confidence: 99%

Exploring the Role of Novel Medical Therapies for Aggressive Pituitary Tumors: A Review of the Literature—“Are We There Yet?”

Lamb

Sim

McCormack

2020

Cancers

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Aggressive pituitary tumors account for up to 10% of pituitary tumors and are characterized by resistance to medical treatment and multiple recurrences despite standard therapies, including surgery, radiotherapy, and chemotherapy. They are associated with increased morbidity and mortality, particularly pituitary carcinomas, which have mortality rates of up to 66% at 1 year after diagnosis. Novel targeted therapies under investigation include mammalian target of rapamycin (mTOR), tyrosine kinase, and vascular endothelial growth factor (VEGF) inhibitors. More recently, immune checkpoint inhibitors have been proposed as a potential treatment option for pituitary tumors. An increased understanding of the molecular pathogenesis of aggressive pituitary tumors is required to identify potential biomarkers and therapeutic targets. This review discusses novel approaches to the management of aggressive pituitary tumors and the role of molecular profiling.

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PTTG overexpression in non-functioning pituitary adenomas: Correlation with invasiveness, female gender and younger age

Cited by 19 publications

References 60 publications

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

Giant Non-Functioning Pituitary Adenoma: Clinical Characteristics and Therapeutic Outcomes

Exploring the Role of Novel Medical Therapies for Aggressive Pituitary Tumors: A Review of the Literature—“Are We There Yet?”

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