Journal Article

Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T‐cell leukemia/lymphoma

Nakachi, Sawako, Fukushima, Takuya, Masuzaki, Hiroaki, Morichika, Kazuho, Nishi, Yukiko, Morishima, Satoko, Ohshiro, Kazuiku, Kayo, Hirona, Okamoto, Shiki, Karube, Kennosuke, Nakazato, Iwao, Uchino, Shuta

2019

Overview

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. In the present study, we investigated the potential role of the STAT3 pathway in adult T‐cell leukemia/lymphoma (ATLL). We carried out immunohistochemistry for activated/phosphorylated STAT3 (pSTAT3) and compared with STAT3 mutation and clinical subtypes of ATLL. We found that the expression of pSTAT3 is detected in ATLL cells except for the lymphoma type, and that the prevalence of cells positive for pSTAT3 correlates with favorable overall and progression‐free survival exclusively in the smoldering type. In contrast, mutation of STAT3 was not significantly correlated with clinicopathological findings in ATLL.

• Publisher: John Wiley and Sons Inc
• Subject: Adult / adult T‐cell leukemia/lymphoma / Aged / Aged, 80 and over / Cell Nucleus - pathology / Female / Humans / immunohistochemistry / Leukemia-Lymphoma, Adult T-Cell - genetics / Leukemia-Lymphoma, Adult T-Cell - mortality / Leukemia-Lymphoma, Adult T-Cell - pathology / Male / Middle Aged / Mutation / Original / phosphorylated STAT3 / Phosphorylation / Prognosis / Progression-Free Survival / Shimoyama classification / STAT3 mutation / STAT3 Transcription Factor - genetics / STAT3 Transcription Factor - metabolism