Concomitant high expression of BRAFV600E, P-cadherin and cadherin 6 is associated with High TNM stage and lymph node metastasis in conventional papillary thyroid carcinoma.
OBJECTIVE
BRAFV600E mutation is the most common activating mutation associated with aggressive behaviours in human tumours including conventional papillary thyroid carcinoma (cPTC). P-cadherin and cadherin 6 have been shown to be mesenchymal-associated cadherins and promote cancer cell invasion and metastasis. The purpose of this study was to examine BRAFV600E, P-cadherin and cadherin 6 expressions in cPTC and to assess the association of their expression with clinicopathological indicators.


METHODS
BRAFV600E, P-cadherin and cadherin 6 protein expressions in 80 cPTCs, 61 nodular hyperplasia and 76 normal thyroid tissues were examined by immunohistochemistry. The correlation of their protein expression with clinicopathological indicators of cPTC was statistically analysed.


RESULTS
Protein expression of BRAFV600E, P-cadherin and cadherin 6 was upregulated in cPTC. High protein expression of BRAFV600E, P-cadherin and cadherin 6 was significantly correlated with high TNM stage and lymph node metastasis (LNM) (P < 0·001). Furthermore, BRAFV600E, P-cadherin and cadherin 6 protein expressions were correlated with one another. BRAFV600E high expression combined with both P-cadherin and cadherin-6 high expressions had stronger correlation with high TNM stage and LNM when compared with BRAFV600E high expression combined with either P-cadherin or cadherin-6 high expression (P = 0·042, 0·017 for TNM stage and P = 0·003, 0·006 for LNM, respectively) and only BRAFV600E high expression (P < 0·001 for both TNM stage and LNM).


CONCLUSIONS
Concomitant high expression of BRAFV600E, P-cadherin and cadherin 6 is strongly associated with high TNM stage and LNM in cPTC.
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Le
L
Zhao
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Rong
R
Jiang
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Man
M
Xu
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Ping
P
Zhu
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Xiao-Mei
XM
Mo
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Ni
N
Wang
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin N.T., Hong Kong, China.
George G
GG
Chen
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Zhi-Min
ZM
Liu
D000328:Adult; D015820:Cadherins / Q000096:biosynthesis*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000096:biosynthesis* / Q000235:genetics; D020125:Mutation, Missense; D009367:Neoplasm Staging; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis* / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
D015820:Cadherins; D050505:Mutant Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C087310:K cadherin