Thyroid cancer is common type of malignant tumor in humans, and the autophagy status of such tumors may vary according to subtype. This study aimed to investigate the expression and implications of the major autophagy-related molecules light chain (LC) 3A, LC3B, p62, and BNIP-3 in human thyroid carcinoma. Tissue microarrays were constructed from 555 thyroid cancers (papillary thyroid carcinoma (PTC): 342; follicular carcinoma (FC): 112; medullary carcinoma (MC): 70; poorly differentiated carcinoma (PDC): 23; and anaplastic carcinoma (AC): 8) and 152 follicular adenomas (FAs). Expression of autophagy-related molecules (LC3A, LC3B, p62, and BNIP-3) was detected immunohistochemically, and the results were analyzed via comparison with clinicopathologic parameters. Tumoral LC3A and LC3B expressions were the highest in MC (p < 0.001), whereas stromal LC3A expression was higher in AC and PTC (p < 0.001). BNIP-3 expression was absent in MC and AC (p = 0.013). Tumoral LC3A, LC3B, and p62 expressions were higher in conventional type PTC, compared with those in the follicular variant. PTC with the BRAF V600E mutation exhibited higher expression of all autophagy-related proteins relative to PTC without this mutation (p < 0.05). BNIP-3 negativity was associated with capsular invasion in FC (p = 0.001), and p62 negativity was associated with lymph node metastasis in MC (p = 0.006). In a univariate analysis, LC3B negativity was associated with shorter disease-free survival in PTC with the BRAF V600E mutation (p = 0.024). We conclude that the expression of autophagy-related proteins differs according to thyroid cancer subtype.
Bibliographical noteFunding Information:
This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Korea (1420080). Additionally, it was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, and Future Planning (2015R1A1A1A05001209).
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry