mTOR pathway and somatostatin receptors expression intratumor-heterogeneity in ileal NETs
| Autor: | Eugenio De Carlo, Giada Munari, Claudio Pasquali, Vittorina Zagonel, Matteo Fassan, Chiara Martini, Carlo Alberto Dal Pozzo, Francesca Bergamo, Roberto Vettor, Chiara Borga, Angelo Paolo Dei Tos, Anna Caterina Milanetto, Sabina Murgioni, Gianmaria Pennelli, Vincenza Guzzardo, Elisabetta Trevellin, Umberto Cillo |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Gene isoform Cancer Research Endocrinology Diabetes and Metabolism Neuroendocrine tumors Metastasis 03 medical and health sciences 0302 clinical medicine Endocrinology Medicine PTEN Humans Receptors Somatostatin PI3K/AKT/mTOR pathway biology Somatostatin receptor business.industry TOR Serine-Threonine Kinases Liver Neoplasms Ribosomal Protein S6 Kinases 70-kDa medicine.disease MicroRNAs Neuroendocrine Tumors 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Immunohistochemistry business NODAL |
| Zdroj: | Endocrine-related cancer. 28(7) |
| ISSN: | 1479-6821 |
| Popis: | The knowledge of the molecular landscape of ileal neuroendocrine tumors (NETs) is affected by the lack of systematic studies investigating intra-tumoral heterogeneity. In this study, intra-tumoral heterogeneity was investigated in 27 primary ileal G1-NETs and their matched nodal and liver metastases in order to assess the tumor grading, the expression status of two somatostatin receptor isoforms (i.e. SSTR2A and SSTR5) and mTOR signaling dysregulation (ph-mTOR, ph-p70S6K, ph-4EBP1, PTEN and miR-21). Among the 27 G1 primary tumors, 4 shifted to G2 in the matched liver metastasis. Although mTOR activation was pretty consistent between primary and secondary malignancies, mTOR effectors (ph-p70S6K and ph-4EBP1) were overexpressed in matched liver metastases, whereas PTEN expression profile changed in only two cases. MiR-21 was significantly up-regulated in the metastatic setting. Although SSTRs expression was present in most of the primary tumors and matched metastasis, we found SSTR5 expression to be significantly increased in liver metastases. Notably, SSTRs expression was heterogeneous within the same lesions in most of the lesions. Overall, despite primary and metastatic ileal NETs show a similar molecular landscape, tumor grading and mTOR signaling pathway may diverge in the metastatic setting, thus affecting prognosis and treatment. |
| Databáze: | OpenAIRE |
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