Prognostic Significance of Altered ATRX/DAXX Gene in Pancreatic Neuroendocrine Tumors: A Meta-Analysis

Wang, Fei; Xu, Xiaowu; Zeng, Ye; Qin, Yi; Lei, Yu; Ji, Shunrong

doi:10.3389/fendo.2021.691557

Cited by 18 publications

(15 citation statements)

References 47 publications

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“…If the expression of ATRX and DAXX is retained, then the prognosis of patients with pancreatic neuroendocrine tumours is improved ( 18 , 19 ). This study is the first to address the expression of these two markers in patients with SPC.…”

Section: Discussionmentioning

confidence: 99%

“…The genes for α-thalassemia/mental retardation syndrome X-linked protein ( ATRX ) and death domain-associated protein ( DAXX ) play important roles in chromatin remodelling at the telomeres and other genomic sites in normal tissues; moreover, whole-exome analysis has revealed that inactivated somatic mutations of these genes are frequently observed in pancreatic neuroendocrine tumours ( 17 ). Subsequent studies have revealed that loss of ATRX and DAXX is associated with chromosomal instability and a shorter survival period in patients with pancreatic neuroendocrine tumours ( 18 , 19 ). However, the frequency of loss of ATRX and DAXX expression and its prognostic significance in SPC patients has not yet been analysed.…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical analyses of the expression profiles of INSM1, ATRX, DAXX and DLL3 in solid papillary carcinomas of the breast

et al. 2022

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Solid papillary carcinoma (SPC) is a rare but distinct clinicopathological feature of breast cancer characterised by frequent neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a useful neuroendocrine marker for various neuroendocrine tumours. α-thalassemia/mental retardation syndrome X-linked protein (ATRX) and death domain-associated protein (DAXX) are useful prognostic markers for patients with pancreatic neuroendocrine tumours. However, to the best of our knowledge, few studies have addressed INSM1 expression in SPCs. Although ATRX, DAXX and δ-like canonical notch ligand 3 (DLL3) are frequently expressed in neuroendocrine lung carcinomas, there are no reports on their expression in SPCs. Therefore, the present study aimed to analyse the expression profiles of INSM1, ATRX, DAXX and DLL3 in the largest series of patients with SPC that has been, to the best of our knowledge, studied until now. Immunohistochemical analyses were performed to determine chromogranin A, synaptophysin, INSM1, ATRX, DAXX and DLL3 expression in 39 specimens surgically resected from patients with SPC (18 SPC in situ and 21 SPC invasive). The associations between the expression of these markers and the clinicopathological factors were investigated. Chromogranin A, synaptophysin and INSM1 were expressed in 64.1, 100 and 92.3% of the patients, respectively. Both ATRX and DAXX expression was observed in 28.2% of the patients. No patient expressed DLL3. Lack of INSM1 or chromogranin A expression was significantly associated with advanced pathological stages in patients with SPC (P=0.033) and in patients with invasive SPC (P=0.012), showing a tendency for a high Ki-67 labelling index (LI) and advanced histological grade in patients with invasive SPC. Loss of ATRX or DAXX expression was significantly associated with lymphatic invasion, but not with histological grade, Ki-67 LI or presence of invasive tumours. Thus, INSM1 was demonstrated to be a useful diagnostic marker for SPCs. Overall, detecting the lack of INSM1 or chromogranin A expression may be useful for analysing the characteristics of tumour cells in SPCs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunohistochemical analyses of the expression profiles of INSM1, ATRX, DAXX and DLL3 in solid papillary carcinomas of the breast

et al. 2022

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“…There is also more clinical value of the finding of ATRX and DAXX gene mutations. In one recent meta-analysis, altered ATRX and DAXX gene had significant correlation with the prognosis of pancreatic NET ( 15 ). Disease- and relapse-free survival significantly decreased in patients who had ATRX and DAXX mutations ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Adaptive Tomotherapy for locally advanced unresectable pancreatic neuroendocrine tumor: Case report and literature review

Huang

Lau

et al. 2022

Front. Oncol.

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BackgroundPancreatic neuroendocrine tumor (NET) is rare, and the majority presents late in their clinical course. Here, we present a huge locally advanced pancreatic NET having Hi-Art helical Tomotherapy that resulted in a 68% reduction in target volume during adaptive image-guided radiotherapy (IGRT).Case summaryA 63-year-old man without any history of systemic disease developed voiding difficulty for several months. Associated symptoms included poor appetite, nausea, distended abdomen, and body weight loss. Further magnetic resonance imaging showed a large multilobulated tumor in the left upper abdomen. Tumor biopsy revealed well-differentiated, grade 2, neuroendocrine tumor. Complete resection was unattainable. Therefore, Lanreotide was prescribed initially. However, tumor progression up to the greatest diameter of 18 cm was noted on computed tomography 5 months later. Thus, he stopped Lanreotide and commenced on concurrent chemoradiotherapy (CCRT). With a total dose of 70 Gy in 35 fractions, we generated two adaptive treatment plans during the whole course. Laparoscopic subtotal pancreatectomy with spleen preservation was performed after neoadjuvant CCRT. It has been more than 3 years after IGRT, and he remains cancer free and reports no side effects during regular follow-ups.ConclusionTomotherapy caused tumor size reduction and hence facilitated surgical possibility for this originally unresectable pancreatic NET. Neoadjuvant IGRT incorporated with adaptive treatment planning enhanced delivery accuracy. In this case of pancreatic NET resistant to Lanreotide, inter-fractional tumor regression from 1910 to 605 cc (68%) was documented.

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“…A loss of DAXX/ATRX is associated with chromosome instability and reduced survival [27]. Recently, a meta-analysis of 14 studies with a total of 2313 patients has supported the prognostic significance of altered DAXX/ATRX genes in pNETs with a combined HR of 5.05 for disease-free survival (95% CI: 1.58-16.20, p = 0.01) [30,31]. In metastatic disease, DAXX/ATRX loss seems to be associated with longer survival.…”

Section: Prognostic Factors In Metastatic Pancreatic Netmentioning

confidence: 99%

Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors—Need for a Conductor

Siebenhüner

Langheinrich

Friemel

et al. 2022

Cancers

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Pancreatic neuroendocrine tumors (pNETs) are a vast growing disease. Over 50% of these tumors are recognized at advanced stages with lymph node, liver, or distant metastasis. An ongoing controversy is the role of surgery in the metastatic setting as dedicated systemic treatments have emerged recently and shown benefits in randomized trials. Today, liver surgery is an option for advanced pNETs if the tumor has a favorable prognosis, reflected by a low to moderate proliferation index (G1 and G2). Surgery in this well-selected population may prolong progression-free and overall survival. Optimal selection of a treatment plan for an individual patient should be considered in a multidisciplinary tumor board. However, while current guidelines offer a variety of modalities, there is so far only a limited focus on the right timing. Available data is based on small case series or retrospective analyses. The focus of this review is to highlight the right time-point for surgery in the setting of the multimodal treatment of an advanced pancreatic neuroendocrine tumor.

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Prognostic Significance of Altered ATRX/DAXX Gene in Pancreatic Neuroendocrine Tumors: A Meta-Analysis

Cited by 18 publications

References 47 publications

Immunohistochemical analyses of the expression profiles of INSM1, ATRX, DAXX and DLL3 in solid papillary carcinomas of the breast

Immunohistochemical analyses of the expression profiles of INSM1, ATRX, DAXX and DLL3 in solid papillary carcinomas of the breast

Adaptive Tomotherapy for locally advanced unresectable pancreatic neuroendocrine tumor: Case report and literature review

Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors—Need for a Conductor

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