title: Expression of Autophagy-Related Proteins in Different Types of Thyroid Cancer.
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.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 130-701, Korea. pinkmin15@yuhs.ac.
authors.forename: Hye Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 130-701, Korea. kesol13@yuhs.ac.
authors.forename: Eun-Sol
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul 130-701, Korea. kjs1976@yuhs.ac.
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D016019:Survival Analysis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D000071183:Autophagy-Related Proteins; C090121:BNIP3 protein, human; C477012:MAP1LC3A protein, human; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: autophagy; pathology; stroma; subtype; thyroid cancer