Abstract
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.
Highlights
Thyroid cancer is common type of malignant tumor, affecting approximately 1% of the total population
Among the various proteins involved in the autophagy process, the following markers are commonly used to evaluate autophagic activity: light chain (LC) 3, which participates in elongation and contributes to autophagosome formation [6,7,8]; p62, a scaffold protein that transfers ubiquitinated proteins to the autophagosome [9,10]; and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), a mitochondrial autophagy regulator [11]
We further evaluated the expression of autophagy-related proteins in papillary thyroid carcinoma (PTC) according to the histologic subtype and BRAF V600E mutation status
Summary
Thyroid cancer is common type of malignant tumor, affecting approximately 1% of the total population. Thyroid cancer manifests as several common subtypes, including papillary thyroid carcinoma (PTC), follicular carcinoma (FC), medullary carcinoma (MC), poorly differentiated carcinoma (PDC), and anaplastic carcinoma (AC). The cellular origin, clinical manifestation, metastatic pattern, and clinical prognosis have been reported to differ depending on the subtype [1]. In the field of cancer research, autophagy, defined as the lysosomal degradation of cellular components, has recently received considerable attention. Autophagy plays an important role in homeostasis through the removal of dysfunctional or damaged cellular components and recycling of necessary cellular components [2,3,4,5]. Among the various proteins involved in the autophagy process, the following markers are commonly used to evaluate autophagic activity: light chain (LC) 3, which participates in elongation and contributes to autophagosome formation [6,7,8]; p62, a scaffold protein that transfers ubiquitinated proteins to the autophagosome [9,10]; and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), a mitochondrial autophagy (mitophagy) regulator [11]
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