Molecular Biomarkers for Progression of Intraductal Papillary Mucinous Neoplasm of the Pancreas
| Autor: | Yuko Kuboki, Masakazu Yamamoto, Kyoko Shimizu, Takashi Hatori, Noriyuki Shibata, Keiko Shiratori, Toru Furukawa |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
Time Factors endocrine system diseases Endocrinology Diabetes and Metabolism DNA Mutational Analysis Kaplan-Meier Estimate medicine.disease_cause Endocrinology Risk Factors GTP-Binding Protein alpha Subunits Gs Phosphorylation Smad4 Protein biology Immunohistochemistry ErbB Receptors Treatment Outcome medicine.anatomical_structure Disease Progression Clinicopathological features KRAS Mitogen-Activated Protein Kinases Pancreas medicine.medical_specialty Proto-Oncogene Proteins p21(ras) Predictive Value of Tests Proto-Oncogene Proteins Pancreatic cancer Biomarkers Tumor Chromogranins Internal Medicine medicine GNAS complex locus Humans Proportional Hazards Models Retrospective Studies Chi-Square Distribution Hepatology Intraductal papillary mucinous neoplasm business.industry medicine.disease Molecular biomarkers Pancreatic Neoplasms Multivariate Analysis Mutation ras Proteins biology.protein Neoplasm Recurrence Local Tumor Suppressor Protein p53 Neoplasms Cystic Mucinous and Serous business |
| Zdroj: | Pancreas. 44:227-235 |
| ISSN: | 0885-3177 |
| Popis: | We aimed to identify molecular biomarkers for assessing the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN).We retrospectively investigated molecular aberrations and their associations with clinicopathological features in 172 IPMNs.GNAS and KRAS mutations were detected in 48% and 56% of IPMNs, respectively. No mutations of EGFR, PIK3CA GNAO1, GNAQ, or GNAI2 were observed. Significant associations were observed between IPMN morphological types and GNAS mutations, KRAS mutations, the expression of phosphorylated MAPK (pMAPK), AKT, and phosphorylated AKT (pAKT), nuclear accumulation of β-catenin, SMAD4 loss, and TP53 overexpression; histological grades and the expression of EGFR, pMAPK, AKT, and pAKT, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression; invasive phenotypes and KRAS mutations, the nuclear β-catenin, and SMAD4 loss; and prognosis and SMAD4 loss and TP53 overexpression. Multivariate analysis to compare prognostic impacts of multiple molecular features revealed that TP53 overexpression was an independent prognostic factor (P = 0.030; hazard ratio, 5.533).These results indicate that mutations in GNAS and KRAS, the expression of EGFR and pMAPK, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression may be relevant for assessing the clinical course of IPMN, including its progression into different morphological types, invasion, and prognosis. |
| Databáze: | OpenAIRE |
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