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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.
PMID
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Authors

Mayor MeshTerms
Keywords

autophagy

pathology

stroma

subtype

thyroid cancer

Journal Title international journal of molecular sciences
Publication Year Start




PMID- 28257096
OWN - NLM
STAT- MEDLINE
DA  - 20170303
DCOM- 20170317
LR  - 20170317
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 3
DP  - 2017 Mar 02
TI  - Expression of Autophagy-Related Proteins in Different Types of Thyroid Cancer.
LID - E540 [pii]
LID - 10.3390/ijms18030540 [doi]
AB  - 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 &lt; 0.001), whereas stromal LC3A
      expression was higher in AC and PTC (p &lt; 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 &lt; 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.
FAU - Kim, Hye Min
AU  - Kim HM
AD  - Department of Pathology, Yonsei University College of Medicine, Seoul 130-701,
      Korea. pinkmin15@yuhs.ac.
FAU - Kim, Eun-Sol
AU  - Kim ES
AD  - Department of Pathology, Yonsei University College of Medicine, Seoul 130-701,
      Korea. kesol13@yuhs.ac.
FAU - Koo, Ja Seung
AU  - Koo JS
AD  - Department of Pathology, Yonsei University College of Medicine, Seoul 130-701,
      Korea. kjs1976@yuhs.ac.
LA  - eng
PT  - Journal Article
DEP - 20170302
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (BNIP3 protein, human)
RN  - 0 (MAP1LC3B protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (P62 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (light chain 3, human)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - Thyroid cancer, medullary
RN  - Thyroid cancer, papillary
SB  - IM
MH  - Adenocarcinoma, Follicular/genetics/metabolism/*pathology
MH  - Autophagy
MH  - Autophagy-Related Proteins/*metabolism
MH  - Carcinoma/genetics/metabolism/*pathology
MH  - Carcinoma, Neuroendocrine/genetics/metabolism/*pathology
MH  - Humans
MH  - Membrane Proteins/metabolism
MH  - Microtubule-Associated Proteins/metabolism
MH  - Mutation
MH  - Prognosis
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - RNA-Binding Proteins/metabolism
MH  - Survival Analysis
MH  - Thyroid Neoplasms/genetics/metabolism/*pathology
MH  - Tissue Array Analysis
OTO - NOTNLM
OT  - autophagy
OT  - pathology
OT  - stroma
OT  - subtype
OT  - thyroid cancer
EDAT- 2017/03/04 06:00
MHDA- 2017/03/18 06:00
CRDT- 2017/03/04 06:00
PHST- 2017/01/03 [received]
PHST- 2017/02/22 [revised]
PHST- 2017/02/24 [accepted]
AID - ijms18030540 [pii]
AID - 10.3390/ijms18030540 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Mar 2;18(3). pii: E540. doi: 10.3390/ijms18030540.

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