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Title :Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T‐cell leukemia/lymphoma
Authors :Morichika, Kazuho
Authors alternative :森近, 一穂
Issue Date :25-Jun-2019
Abstract :Adult T‐cell leukemia/lymphoma (ATLL) is a mature T‐cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. Based on previous integrated molecular analyses suggesting the importance of the JAK‐STAT pathway in ATLL, we attempted to clarify the clinicopathological significance of this pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6 were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Expression of pSTAT3 was observed in 43% (50/116) of ATLL cases, whereas pSTAT5 and pSTAT6 were largely undetected. Cases with the lymphoma type showed significantly less frequent pSTAT3 expression (8/45, 18%) than those with the other subtypes (41/66, 62%; P < .001). STAT3 mutations were detected in 36% (10/28) and 19% (12/64) of cases with the smoldering and aggressive types of ATLL, respectively. The correlation between STAT3 mutation and pSTAT3 expression was not significant (P = .07). Both univariate and multivariate analysis revealed that pSTAT3 expression was significantly associated with better overall survival and progression‐free survival in the smoldering type of ATLL, whereas STAT3 mutation was not related to a line of clinical outcome. Collectively, our data show that only the lymphoma type showed a low prevalence of tumor cells positive for pSTAT3 expression, and raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.
URL :https://doi.org/10.1111/cas.14114
Type Local :学位論文
ISSN :1347-9032
1349-7006
Publisher :University of the Ryukyus
URI :http://hdl.handle.net/20.500.12000/46668
Grant id :18001医研第501号
Date of granted :2020-03-24
Degree name :博士(医学)
Grantor :琉球大学
Citation :Cancer Science Vol.110 no.9 p.2982 -2991
Appears in Collections:Doctoral Dissertation (Graduate School of Medicine)

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