ArticleBMC cancer2020
P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Oral and Maxillofacial Neuroendocrine Carcinoma: A Systematic Review.Head and neck pathology · 2022Pooled it
- Diagnostic relevance of p53 and Rb status in neuroendocrine tumors G3 from different organs: an immunohistochemical study of 465 high-grade neuroendocrine neoplasms.Virchows Archiv : an international journal of pathology · 2025Article
- Patterns and outcomes of current antitumor therapy for high-grade neuroendocrine neoplasms: perspective of a tertiary referral center.Journal of cancer research and clinical oncology · 2025Article
- Prognostic and predictive significance of p53 and ATRX in neuroendocrine neoplasms of GIT and pancreas and their utility as an adjunct to accurate diagnosis-An eight-year retrospective study.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025Article
- SCG2 and CPE may be novel markers for the identification of pancreatic neuroendocrine tumors and solid pseudopapillary neoplasms.Translational cancer research · 2024Article
- [Practical application of immunohistochemistry in pancreatic neuroendocrine neoplasms : Tips and pitfalls].Pathologie (Heidelberg, Germany) · 2024Review
- Clinicopathological correlations in 38 cases of gastroenteropancreatic high-grade neuroendocrine neoplasms.Frontiers in oncology · 2024Article
- Article
- Article
- A systematic review of therapeutic strategies in gastroenteropancreatic grade 3 neuroendocrine tumors.Therapeutic advances in medical oncology · 2023Review
- Risk Stratification of Pancreatic Neuroendocrine Neoplasms Based on Clinical, Pathological, and Molecular Characteristics.Journal of clinical medicine · 2022Review
- Peptide Receptor Radionuclide Therapy.The Journal of clinical endocrinology and metabolism · 2022Article
- Is There a Role for Surgical Resection of Grade 3 Neuroendocrine Neoplasms?Annals of surgical oncology · 2022Article
- Review
- Prognostic factors of primary neuroendocrine breast cancer: A population-based study.Cancer medicine · 2022Article
- Role of Somatostatin Signalling in Neuroendocrine Tumours.International journal of molecular sciences · 2022Review
- Somatostatin and Its Receptor System in Colorectal Cancer.Biomedicines · 2021Review
- The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5.Experimental and therapeutic medicine · 2021Article
- A Subset of Large Cell Neuroendocrine Carcinomas in the Gastroenteropancreatic Tract May Evolve from Pre-existing Well-Differentiated Neuroendocrine Tumors.Endocrine pathology · 2021Article
- Prognostic significance of CEA, Ki67 and p53 in pseudomyxoma peritonei of appendiceal origin.The Journal of international medical research · 2021Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) with a Ki67 proliferation index > 20%, include well-differentiated tumours grade 3 (NET G3) and poorly differentiated (PD) neuroendocrine carcinomas (NEC). Abnormal p53-expression is a feature of PD tumours, while expression of chromogranin A (CgA) and somatostatin-receptor 2a (SSTR-2a) may be a feature of well-differentiated tumours. The aim of this study was to elucidate the expression and prognostic value of these three markers in 163 GEP-NEN patients with a Ki67-index > 20%.
methodClinical data, histopathology and overall survival were analysed according to Kaplan-Meier's method and Cox regression. The expression of SSTR-2a, CgA and synaptophysin was analysed in tumour specimens by immunohistochemistry, and semi-quantitatively scored as negative (< 5%), heterogeneously positive (5-30%) or strongly positive (> 30%). P53 was defined as normal when scored as heterogeneously positive (1-30%), and abnormal when negative (0%) or strongly positive (> 30%).
resultsIn multivariate analysis, better survival was observed among patients with heterogeneously positive p53 compared to strongly positive (p < 0.001). When dichotomised, tumours with a heterogeneously positive p53 vs. negative and strongly positive p53 also showed a significantly better survival (p = 0.002). Survival was significantly worse for negative CgA compared to heterogeneously positive CgA (p = 0.02). Strongly positive SSTR-2a expression was found in 26% of the 163 included patients. Well-differentiated morphology correlated with strong expression of SSTR-2a and CgA, and heterogeneously positive p53-staining, and was more frequent in pancreatic primaries. In pancreatic primaries, strongly positive SSTR-2a was associated with longer survival (univariate analysis, p = 0.02). A significantly lower Ki67 proliferation index was found in patients with a heterogeneously positive p53, a positive SSTR-2a and CgA expression.
conclusionOur results suggest that abnormal p53-expression is an independent negative prognostic marker in GEP-NEN with a Ki67-index > 20%. Patients with heterogeneously positive p53 had the best prognosis. SSTR-2a was a positive prognostic marker in pancreatic NEN. Negative CgA was associated with a significantly worse OS compared to heterogeneously positive CgA-expression in a multivariate sub-analysis. Lower Ki67 index correlated significantly with heterogeneously positive p53, positive SSTR-2a and CgA expression.
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