Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management-An Updated Review

Overview

Journal Front Oncol

Specialty Oncology

Date 2020 Jun 16

PMID 32537434

Citations 19

Authors

Martine Bocchini

Fabio Nicolini

Stefano Severi

Alberto Bongiovanni

Toni Ibrahim

Giorgia Simonetti

Ilaria Grassi

Massimiliano Mazza

Affiliations

Soon will be listed here.

Abstract

Pancreatic neuroendocrine tumors (PanNENs) are rare sporadic cancers or develop as part of hereditary syndromes. PanNENs can be both functioning and non-functioning based on whether they produce bioactive peptides. Some PanNENs are well differentiated while others-poorly. Symptoms, thus, depend on both oncological and hormonal causes. PanNEN diagnosis and treatment benefit from and in some instances are guided by biomarker monitoring. However, plasmatic monoanalytes are only suggestive of PanNEN pathological status and their positivity is typically followed by deepen diagnostic analyses through imaging techniques. There is a strong need for new biomarkers and follow-up modalities aimed to improve the outcome of PanNEN patients. Liquid biopsy follow-up, i.e., sequential analysis on tumor biomarkers in body fluids offers a great potential, that need to be substantiated by additional studies focusing on the specific markers and the timing of the analyses. This review provides the most updated panorama on PanNEN biomarkers.

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References

Thakker R . Multiple endocrine neoplasia type 1 (MEN1). Best Pract Res Clin Endocrinol Metab. 2010; 24(3):355-70. DOI: 10.1016/j.beem.2010.07.003. View

Bodei L, Kidd M, Singh A, van der Zwan W, Severi S, Drozdov I . PRRT neuroendocrine tumor response monitored using circulating transcript analysis: the NETest. Eur J Nucl Med Mol Imaging. 2019; 47(4):895-906. PMC: 7515632. DOI: 10.1007/s00259-019-04601-3. View

Li S, Essaghir A, Martijn C, Lloyd R, Demoulin J, Oberg K . Global microRNA profiling of well-differentiated small intestinal neuroendocrine tumors. Mod Pathol. 2013; 26(5):685-96. PMC: 3647117. DOI: 10.1038/modpathol.2012.216. View

Sadanandam A, Wullschleger S, Lyssiotis C, Grotzinger C, Barbi S, Bersani S . A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics. Cancer Discov. 2015; 5(12):1296-313. PMC: 4946251. DOI: 10.1158/2159-8290.CD-15-0068. View

Pizzi S, Azzoni C, Bottarelli L, Campanini N, DAdda T, Pasquali C . RASSF1A promoter methylation and 3p21.3 loss of heterozygosity are features of foregut, but not midgut and hindgut, malignant endocrine tumours. J Pathol. 2005; 206(4):409-16. DOI: 10.1002/path.1784. View

Toumpanakis C, Kim M, Rinke A, Bergestuen D, Thirlwell C, Khan M . Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors. Neuroendocrinology. 2014; 99(2):63-74. DOI: 10.1159/000358727. View

Borsari S, Pardi E, Pellegata N, Lee M, Saponaro F, Torregrossa L . Loss of p27 expression is associated with MEN1 gene mutations in sporadic parathyroid adenomas. Endocrine. 2016; 55(2):386-397. DOI: 10.1007/s12020-016-0941-6. View

Severi S, Nanni O, Bodei L, Sansovini M, Ianniello A, Nicoletti S . Role of 18FDG PET/CT in patients treated with 177Lu-DOTATATE for advanced differentiated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013; 40(6):881-8. DOI: 10.1007/s00259-013-2369-z. View

Oberg K, Modlin I, de Herder W, Pavel M, Klimstra D, Frilling A . Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015; 16(9):e435-e446. PMC: 5023063. DOI: 10.1016/S1470-2045(15)00186-2. View

10.

Thorns C, Schurmann C, Gebauer N, Wallaschofski H, Kumpers C, Bernard V . Global microRNA profiling of pancreatic neuroendocrine neoplasias. Anticancer Res. 2014; 34(5):2249-54. View

11.

Yazdani S, Kasajima A, Ogata H, Felizola S, Nakamura Y, Onodera Y . Progesterone Receptor Isoforms A and B in Pancreatic Neuroendocrine Tumor. Neuroendocrinology. 2015; 101(4):309-20. DOI: 10.1159/000381455. View

12.

Scarpa A, Chang D, Nones K, Corbo V, Patch A, Bailey P . Whole-genome landscape of pancreatic neuroendocrine tumours. Nature. 2017; 543(7643):65-71. DOI: 10.1038/nature21063. View

13.

Makuuchi R, Terashima M, Kusuhara M, Nakajima T, Serizawa M, Hatakeyama K . Comprehensive analysis of gene mutation and expression profiles in neuroendocrine carcinomas of the stomach. Biomed Res. 2017; 38(1):19-27. DOI: 10.2220/biomedres.38.19. View

14.

Missiaglia E, Dalai I, Barbi S, Beghelli S, Falconi M, Della Peruta M . Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway. J Clin Oncol. 2009; 28(2):245-55. PMC: 4288616. DOI: 10.1200/JCO.2008.21.5988. View

15.

Wang Y, Wang W, Jin K, Fang C, Lin Y, Xue L . Somatostatin receptor expression indicates improved prognosis in gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting release is effective and safe in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors. Oncol Lett. 2017; 13(3):1165-1174. PMC: 5403486. DOI: 10.3892/ol.2017.5591. View

16.

Filosso P, Kidd M, Roffinella M, Lewczuk A, Chung K, Kolasinska-Cwikla A . The utility of blood neuroendocrine gene transcript measurement in the diagnosis of bronchopulmonary neuroendocrine tumours and as a tool to evaluate surgical resection and disease progression. Eur J Cardiothorac Surg. 2017; 53(3):631-639. DOI: 10.1093/ejcts/ezx386. View

17.

Francis J, Lin W, Rozenblatt-Rosen O, Meyerson M . The menin tumor suppressor protein is phosphorylated in response to DNA damage. PLoS One. 2011; 6(1):e16119. PMC: 3021530. DOI: 10.1371/journal.pone.0016119. View

18.

Stefanoli M, La Rosa S, Sahnane N, Romualdi C, Pastorino R, Marando A . Prognostic relevance of aberrant DNA methylation in g1 and g2 pancreatic neuroendocrine tumors. Neuroendocrinology. 2014; 100(1):26-34. DOI: 10.1159/000365449. View

19.

Furlan D, Sahnane N, Mazzoni M, Pastorino R, Carnevali I, Stefanoli M . Diagnostic utility of MS-MLPA in DNA methylation profiling of adenocarcinomas and neuroendocrine carcinomas of the colon-rectum. Virchows Arch. 2012; 462(1):47-56. DOI: 10.1007/s00428-012-1348-2. View

20.

Ikeda M, Okuyama H, Takahashi H, Ohno I, Shimizu S, Mitsunaga S . Chemotherapy for advanced poorly differentiated pancreatic neuroendocrine carcinoma. J Hepatobiliary Pancreat Sci. 2015; 22(8):623-7. DOI: 10.1002/jhbp.228. View