LIMD2 Is Overexpressed in BRAF V600E-Positive Papillary Thyroid Carcinomas and Matched Lymph Node Metastases

Author(s)

Carregosa Pinheiro dos Santos, Maria Jose ^[1] ; Bastos, Andre Uchimura ^[1] ; da Costa, Vitor Rodrigues ^[1] ; Delcelo, Rosana ^[2] ; Lindsey, Susan Chow ^[3] ; Colozza-Gama, Gabriel Avelar ^[1] ; Peng, Hongzhuang ^{[4, 5]} ; Rauscher, III, Frank J. ; Oler, Gisele ^[1] ; Cerutti, Janete Maria ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Genet Bases Thyroid Tumors Lab, Dept Morphol & Genet, Rua Pedro Toledo 669, 11 Andar, Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Pathol, Rua Botucatu 740, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Lab Mol & Translat Endocrinol, Dept Med, Rua Pedro Toledo 669, 11 Andar, Sao Paulo, SP - Brazil

^[4] III, Univ Penn, Wistar Inst, 3601 Spruce St, Philadelphia, PA 19104 - USA

^[5] III, Vet Affairs Med Ctr, 3601 Spruce St, Philadelphia, PA - USA

• Document type: Journal article
• Source: ENDOCRINE PATHOLOGY; v. 29, n. 3, p. 222-230, SEP 2018.
• Web of Science Citations: 3

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. (AU)

• FAPESP's process: 14/06570-6 - Comprehensive whole exome, paired-end RNA and genome sequencing: new insights into genetic bases of thyroid carcinoma in pediatric and adult ages and applications in clinical practice
• Grantee: Janete Maria Cerutti
• Support Opportunities: Research Projects - Thematic Grants