Expression of activated Notch1 and Hey1 in papillary thyroid carcinoma

• Published in: Histopathology 2017-01, Vol.70 (2), p.301-308
• Main Authors: Jung, Chang Won, Kong, Jun Suk, Seol, Hyesil, Park, Sunhoo, Koh, Jae Soo, Lee, Seung‐Sook, Kim, Min Joo, Choi, Ik Joon, Myung, Jae Kyung
• Format: Article
• Language: English
• Subjects: activated Notch1; Adult; Aged; Basic Helix-Loop-Helix Transcription Factors - analysis; Basic Helix-Loop-Helix Transcription Factors - biosynthesis; Biomarkers, Tumor - analysis; Carcinoma - pathology; Carcinoma, Papillary; Cell Cycle Proteins - analysis; Cell Cycle Proteins - biosynthesis; Female; Hey1; Humans; Immunohistochemistry; Lymphatic system; Male; Metastasis; Middle Aged; Multivariate analysis; papillary thyroid carcinoma; Receptor, Notch1 - analysis; Receptor, Notch1 - biosynthesis; Thyroid cancer; Thyroid Cancer, Papillary; Thyroid Neoplasms - pathology; Tissue Array Analysis; Young Adult
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.13065

Aims The Notch signalling pathway is involved in normal development as well as tumorigenesis. However, it is unclear whether Notch activation is related to diverse clinicopathological factors in papillary thyroid carcinoma (PTC). Methods and results We examined the relationship between clinicopathological factors and the expression of activated Notch1 and Hey1, which are indicators of Notch signalling pathway activation, in 109 PTC cases. Activated Notch1 showed strong, moderate and weak expression in 23, 48 and 36 cases, respectively. Its expression was related significantly to histopathological variants (P = 0.007), lymph node metastasis (P = 0.016), BRAF mutation (P = 0.036) and extent of surgery (P = 0.014). Hey1 immunostaining could be divided into two groups: positive and negative, with 26 and 83 cases, respectively. Its expression was related significantly to histopathological variants (P = 0.026), extrathyroidal extension (P = 0.005), BRAF mutation (P = 0.048) and recurrence or soft tissue metastasis (P = 0.000). Multivariate analysis revealed that tumour size (>1 cm), Hey1 immunoreactivity and the presence of lymph node metastasis were associated significantly with recurrence or soft tissue metastasis (odds ratio = 7.38, 4.28 and 12.00, respectively). Conclusions Thus, we found that activation of Notch signalling was correlated significantly with clinicopathological parameters. Therefore, Notch signalling could be a useful prognostic marker in patients with PTC.