Endocrine Tumors Display Site-Specific Alterations in Wnt Signaling, the mTOR Pathway, and Chromatin Remodeling
Paula S Ginter, Nicole C Panarelli, Rhonda K Yantiss, Theresa Scognamiglio, Yao-Tseng Chen. Weill Cornell Medical College, New York
Background: Endocrine tumors (ET) comprise a heterogeneous group of neoplasms that affect multiple organ systems, yet genetic alterations in these sporadic tumors are poorly defined. Some ET of the bronchi, gastrointestinal (GI) tract, and adrenal cortex show B-catenin mutations, whereas mTOR pathway activation and mutations in the chromatin remodeling genes, ATRX and DAXX, are thought to be crucial to pancreatic ET pathogenesis. In this study, we evaluated the expression of B-catenin, mTOR pathway proteins, ATRX and DAXX in ET from various organs to determine their potential roles in the pathogenesis of ET.
Design: Tissue microarrays were constructed from low-to-intermediate grade ET (Ki-67 index <20%), including 50 parathyroid adenomas, 50 adrenocortical adenomas, 46 pituitary adenomas, 51 bronchial carcinoid tumors, and 60 well-differentiated ET of the GI tract [27 small intestinal, 10 appendiceal, and 23 pancreatic]. TMAs were stained for B-catenin, p-mTOR, PTEN, TSC2, ATRX and DAXX. Aberrant staining was defined as nuclear staining for B-catenin, increased (2+ to 3+) cytoplasmic mTOR staining, decreased (0 to 1+) cytoplasmic staining for TSC2 and PTEN, and staining of <50% of nuclei for ATRX and DAXX.
|Small Intestinal ET (n=27)||Appendiceal ET (n=10)||Pancreatic ET (n=23)||Bronchial Carcinoid (n=51)||Adrenocortical Adenoma (n=50)||Pituitary Adenoma (n=46)||Parathyroid adenoma (n=50)|