LIMD2 Is Overexpressed in BRAF V600E-Positive Papillary Thyroid Carcinomas and Matched Lymph Node Metastases |
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Authors: | Maria José Carregosa Pinheiro dos Santos André Uchimura Bastos Vitor Rodrigues da Costa Rosana Delcelo Susan Chow Lindsey Gabriel Avelar Colozza-Gama Hongzhuang Peng III" target="_blank">Frank J RauscherIII Gisele Oler Janete Maria Cerutti |
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Institution: | 1.Genetic Bases of Thyroid Tumors Laboratory, Department of Morphology and Genetics,Universidade Federal de S?o Paulo,S?o Paulo,Brazil;2.Department of Pathology,Universidade Federal de S?o Paulo,S?o Paulo,Brazil;3.Laboratory of Molecular and Translational Endocrinology, Department of Medicine,Universidade Federal de S?o Paulo,S?o Paulo,Brazil;4.The Wistar Institute,University of Pennsylvania and Veterans Affairs Medical Center,Philadelphia,USA |
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Abstract: | We previously described that LIM domain containing 2 (LIMD2) overexpression was closely correlated with metastatic process in papillary thyroid carcinoma (PTC). We here evaluated the expression of LIMD2 in a series of non-metastatic and metastatic PTC and their matched lymph node metastases via immunohistochemistry. LIMD2 was expressed in 74 (81%) of primary PTC and 35 (95%) of lymph node metastases. Sub-analysis performed in 37 matched samples demonstrated that in four cases, LIMD2 is expressed in lymph node metastases, while it is not expressed in primary tumors. Moreover, in eight cases, the staining intensity of LIMD2 was stronger in the patient-matched lymph node metastases than in the primary tumors. Next, the expression of LIMD2 was correlated with clinical pathological parameters and BRAF V600E and RET/PTC mutational status. The expression of LIMD2 in primary tumors was correlated with the presence of BRAF V600E mutation (P =?0.0338). Western blot analysis in thyroid cell lines demonstrated that LIMD2 is expressed in two PTC cell lines, while it is not expressed in normal thyroid and follicular thyroid carcinoma cell lines. Importantly, its expression was higher in a PTC cell line that harbors BRAF V600E mutation than in a PTC cell line that harbors RET/PTC1. The available genomic profiling data generated by The Cancer Genome Atlas Research Network confirmed that LIMD2 expression is higher in BRAF-like PTC samples. Our data suggest that LIMD2 may play an important role in the metastatic process of PTC, predominantly in BRAF V600E-positive tumors. |
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