The p75 neurotrophin receptor is widely expressed in conventional papillary thyroid carcinoma.
Papillary thyroid carcinomas (PTCs) are associated with alterations in several proto-oncogenes related with nervous system development and function, such as TrkA and RET, which are commonly rearranged in these carcinomas. The other oncogenic event recently identified in PTC is the BRAF V600E mutation. Because the role of TrkA was not completely elucidated in thyroid cancer ethiopathogenesis, we decided to study the expression of active, phosphorylated TrkA and of its coreceptor p75 neurotrophin receptor (p75 NTR) in a series of 92 PTC (37 lesions of conventional PTC, 28 of follicular variant of PTC [FVPTC], and 27 of other variants of PTC) as well as in 21 samples of normal thyroid and nonneoplastic thyroid lesions used as a controls. We observed neoexpression of p75 NTR in PTC, particularly in conventional PTC and in other variants of PTC displaying a papillary growth pattern, rather than in FVPTC. No immunoexpression of p75 NTR was observed in normal thyroid nor in nonneoplastic thyroid lesions. The cellular localization of p75 NTR immunoexpression was also significantly associated with the growth pattern of PTC, being much more frequently detected in an apical localization in PTC with papillary architecture than in PTC with a follicular or solid growth pattern. This apical localization of p75 NTR was significantly associated with the presence of BRAF V600E. No significant differences were detected between normal thyroid, nonneoplastic lesions, and PTC (or any PTC variant) regarding expression/activation of TrkA, thus suggesting that by itself and in contrast to p75 NTR, TrkA is not altered during PTC development.
Rocha
Ana Sofia
AS
IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
Risberg
Björn
B
Magalhães
João
J
Trovisco
Vitor
V
de Castro
Inês Vieira
IV
Lazarovici
Philip
P
Soares
Paula
P
Davidson
Ben
B
Sobrinho-Simões
Manuel
M
D000231:Adenocarcinoma, Papillary / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf