TY - JOUR
T1 - Activation of STAT3 in thymic epithelial tumours correlates with tumour type and clinical behaviour
AU - Chang, K. C.
AU - Wu, M. H.
AU - Jones, D.
AU - Chen, F. F.
AU - Tseng, Y. L.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/10
Y1 - 2006/10
N2 - The STAT3 (signal transducers and activators of transcription 3) signalling pathway plays a pivotal role in oncogenesis and appears essential for postnatal maintenance of thymic architecture and thymocyte survival. The association of STAT3 activation with thymic epithelial tumours (TETs) and myasthenia gravis (MG) has not been elucidated. In this study, 118 cases of TET and 25 non-neoplastic thymic tissue samples were evaluated for STAT3 and phospho-STAT3 (pSTAT3) expression immunohistochemically. In addition, 44 normal thymuses of different ages were included for comparison. It was found that STAT3 activation in thymic epithelial cells (TECs), as evidenced by pSTAT3 expression and/or nuclear STAT3, was present in the majority of non-neoplastic thymuses (88%, 22/25), including those from young children, but not in fetal thymus. In thymoma (n = 73), activated STAT3 was noted at a significantly higher frequency in the cases of lymphocyte-rich thymoma (ie types AB, B1, and B2, 46%, 23/50) in comparison with lymphocyte-depleted thymoma (types A and B3, 1/23) (p = 0.009). Thymoma with activated STAT3 tended to present at an earlier stage, show complete resectability and less aggressive behaviour, and have a higher correlation with MG than the STAT3-negative/inactive group (p < 0.05). In contrast, thymic carcinoma with activated STAT3 (14/45, 31 %) had significantly higher rates of unresectability, vascular invasion, and regional lymph node metastasis (p < 0.05). These data provide the first evidence that constitutive STAT3 activation is seen in both benign and neoplastic thymic tissue and is associated with the persistence of thymic tissue and the presence of MG. It is likely to be induced by different factors in thymoma and thymic carcinoma.
AB - The STAT3 (signal transducers and activators of transcription 3) signalling pathway plays a pivotal role in oncogenesis and appears essential for postnatal maintenance of thymic architecture and thymocyte survival. The association of STAT3 activation with thymic epithelial tumours (TETs) and myasthenia gravis (MG) has not been elucidated. In this study, 118 cases of TET and 25 non-neoplastic thymic tissue samples were evaluated for STAT3 and phospho-STAT3 (pSTAT3) expression immunohistochemically. In addition, 44 normal thymuses of different ages were included for comparison. It was found that STAT3 activation in thymic epithelial cells (TECs), as evidenced by pSTAT3 expression and/or nuclear STAT3, was present in the majority of non-neoplastic thymuses (88%, 22/25), including those from young children, but not in fetal thymus. In thymoma (n = 73), activated STAT3 was noted at a significantly higher frequency in the cases of lymphocyte-rich thymoma (ie types AB, B1, and B2, 46%, 23/50) in comparison with lymphocyte-depleted thymoma (types A and B3, 1/23) (p = 0.009). Thymoma with activated STAT3 tended to present at an earlier stage, show complete resectability and less aggressive behaviour, and have a higher correlation with MG than the STAT3-negative/inactive group (p < 0.05). In contrast, thymic carcinoma with activated STAT3 (14/45, 31 %) had significantly higher rates of unresectability, vascular invasion, and regional lymph node metastasis (p < 0.05). These data provide the first evidence that constitutive STAT3 activation is seen in both benign and neoplastic thymic tissue and is associated with the persistence of thymic tissue and the presence of MG. It is likely to be induced by different factors in thymoma and thymic carcinoma.
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U2 - 10.1002/path.2041
DO - 10.1002/path.2041
M3 - Article
C2 - 16917804
AN - SCOPUS:33749046082
VL - 210
SP - 224
EP - 233
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 2
ER -