Reproducing the molecular subclassification of peripheral T-cell lymphoma–NOS by immunohistochemistry

Amador-Ortiz, Catalina; Greiner, Timothy C.; Heavican, Tayla B.; Smith, Lynette M.; Galvis, Karen; Lone, Waseem; Bouska, Alyssa; d’Amore, Francesco; Pedersen, Martin Bjerregård; Pileri, Stefano; Agostinelli, Claudio; Feldman, Andrew L.; Rosenwald, Andreas; Ott, German; Mottok, Anja; Savage, Kerry J.; Leval, Laurence de; Gaulard, Philippe; Lim, Soon Thye; Ong, Choon Kiat; Ondrejka, Sarah L.; Song, Joo Y.; Campo, Elı́as; Jaffe, Elaine S.; Staudt, Louis M.; Rimsza, Lisa M.; Vose, Julie M.; Weisenburger, Dennis D.; Chan, Wing C.; Iqbal, Javeed

doi:10.1182/blood.2019000779

Cited by 123 publications

(106 citation statements)

References 41 publications

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“…Another mechanism of STAT3 activation is possible through the deregulation of suppressors of the JAK/STAT pathway such as SOCS3 [40] leading to constitutive STAT activation and oncogenesis. In addition, further studies are needed to combine any association with JAK-STAT pathway activation and expression of essential transcription factors such as GATA3 and Tbet, which define new subclasses of PTCL-NOS with prognostic consequences, where GATA3 signatures are associated with worse prognosis [41,42].…”

Section: Discussionmentioning

confidence: 99%

STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK− ALCL

Andersson

Brück

Braun

et al. 2020

Cancers

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Peripheral T-cell lymphomas (PTCL) are a heterogeneous, and often aggressive group of non-Hodgkin lymphomas. Recent advances in the molecular and genetic characterization of PTCLs have helped to delineate differences and similarities between the various subtypes, and the JAK/STAT pathway has been found to play an important oncogenic role. Here, we aimed to characterize the JAK/STAT pathway in PTCL subtypes and investigate whether the activation of the pathway correlates with the frequency of STAT gene mutations. Patient samples from AITL (n = 30), ALCL (n = 21) and PTCL-NOS (n = 12) cases were sequenced for STAT3, STAT5B, JAK1, JAK3, and RHOA mutations using amplicon sequencing and stained immunohistochemically for pSTAT3, pMAPK, and pAKT. We discovered STAT3 mutations in 13% of AITL, 13% of ALK + ALCL, 38% of ALK − ALCL and 17% of PTCL-NOS cases. However, no STAT5B mutations were found and JAK mutations were only present in ALK -ALCL (15%). Concurrent mutations were found in all subgroups except ALK + ALCL where STAT3 mutations were always seen alone. High pY-STAT3 expression was observed especially in AITL and ALCL samples. When studying JAK-STAT pathway mutations, pY-STAT3 expression was highest in PTCLs harboring either JAK1 or STAT3 mutations and CD30 + phenotype representing primarily ALK − ALCLs. Further investigation is needed to elucidate the molecular mechanisms of JAK-STAT pathway activation in PTCL.Cancers 2020, 12, 702 2 of 17 diagnoses [1]. The most prevalent PTLCs are PTCL not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-negative (ALK − ALCL), and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK + ALCL) [2,3].Despite generally favorable response rates to chemotherapy, remissions are often not durable, and as such the natural history of PTCL is characterized by relapses and refractory disease. For this reason, upfront hematopoietic stem cell transplantation (HSCT) is often recommended in first remission for patients who are fit and have chemo-sensitive disease [4]. For patients who are not suitable for transplantation, chances of long-term disease control are very limited, with an average progression-free survival (PFS) of 5.5 months [5]. In this setting, optimal therapeutic approaches remain undefined representing an unmet clinical need.Recent advances in the molecular and genetic characterization of PTCL have helped to delineate differences and similarities between the various subtypes [6]. Several recurrent mutations have been identified in small subsets of patients potentially enabling more accurate disease classification and guide treatment decisions. In AITL, the three most commonly identified genetic lesions occur in the Tet methylcytosine dioxygenase 2 gene (TET2), the Ras homolog gene family, member A (RHOA), and the isocitrate dehydrogenase 2 gene (IDH2). Besides AITL, TET2 mutations can be seen with a high frequency also in PTCL-NOS with a T follicular helper cell phenotype [7]. RHOA, a small GTPase participating i...

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Section: Discussionmentioning

confidence: 99%

STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK− ALCL

Andersson

Brück

Braun

et al. 2020

Cancers

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“…Approximately one-third of CTCLs are designated as pcPTCL-NOS [17]. Gene expression profiling may be helpful to define two major molecular subtypes of pcPTCL-NOS, pcPTCL-GATA3 and pcPTCL-TBX21, which have distinct biological differences and poorer prognosis in pcPTCL-GATA3 [17]. In our study, there were eight cases (13.5% of non-MF/SS CLs and 24.2% of primary CTCLs) classified into pcPTCL-NOS (Table 1).…”

Section: Demographic Profiles and Comparisons Of Global Regional Diffmentioning

confidence: 99%

Non-mycosis fungoides cutaneous lymphomas in a referral center in Taiwan: A retrospective case series and literature review

Liu

Tsai²,

Lee

2020

PLoS ONE

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Background While mycosis fungoides (MF) and Sé zary syndrome (SS) are the most common cutaneous lymphomas (CLs), there is limited data about non-MF/SS CLs. Objective We aimed to evaluate clinical characteristics of non-MF/SS CLs. Methods A retrospective analysis evaluated patients with non-MF/SS CLs covering a period of 17 years. The records of 59 patients with non-MF/SS CLs were reviewed for demographic profiles, clinical features, and survival outcomes. Results Our series consisted of 38 non-MF/SS cutaneous T-cell lymphomas (CTCLs) and 21 cutaneous B-cell lymphomas (CBCLs). In the group of non-MF/SS CTCLs including 33 primary and five secondary cases, there were cases of anaplastic large cell lymphoma (15.3% of non-MF/SS CLs), extranodal natural killer/ T-cell lymphoma (13.5%), peripheral T-cell lymphoma, not otherwise specified (13,5%), adult T-cell leukemia/lymphoma (8.5%), subcutaneous panniculitis-like T-cell lymphoma (6.8%) and angioimmunoblastic T-cell lymphoma (6.8%). In the group of CBCLs including nine primary and 12 secondary cases, there were cases of diffuse large B-cell lymphoma (22.0%), mantle cell lymphoma (5.1%), extranodal marginal lymphoma of mucosa associated lymphoid tissue (3.4%), follicle center lymphoma (3.4%) and intravascular large B-cell lymphoma (1.7%). The overall survivals were 57 months for non-MF/SS CTCLs and 41.5 months for CBCLs. Elevated serum lactate dehydrogenase level, thrombocytopenia, multiple anatomical sites of skin involvement and lower albumin level may be associated with poor prognosis in non-MF/SS CTCLs, but the latter two were not in CBCLs.

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“…The treatment can include an estrogen antagonist (when oestrogen receptors are overexpressed), a monoclonal antibody that blocks HER2 activity (when HER2 gene is amplified), or chemotherapy (when the grade, TNM stage, or gene expression profile indicates a high risk of relapse [14]). Another example with expected clinical application is the case of peripheral T cell lymphomas not otherwise specified: this heterogeneous group of lymphomas has recently been subclassified, on the basis of gene and protein expression profiles, into two subtypes with distinct prognoses [15]. Thus, molecular information is helping to distinguish tumors into subtypes for which different treatments can be developed.…”

Section: Impact Of Molecular-genetic Data On Tumor Classification Andmentioning

confidence: 99%

Cancer Classification at the Crossroads

Carbone

2020

Cancers

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Internationally accepted classifications of malignant tumors, developed by the World Health Organization (WHO) and the Union for International Cancer Control (UICC), are based on the histotype, site of origin, morphologic grade, and spread of cancer throughout the body. The WHO classifications are the foundation of cancer diagnosis and the starting point for cancer management. Starting in 2000, the WHO classifications began to include biologic and molecular–genetic features. These developments are having a strong impact on cancer diagnosis and treatment, and this impact is amplifying, given the advances in cancer genomics. Molecular–genetic profiling can be used to refine existing classifications of tumors and, for a small but increasing number of cancers, even determine the treatment irrespective of histotype. Here I discuss how cancer classifications may change in the era of cancer genomics.

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Reproducing the molecular subclassification of peripheral T-cell lymphoma–NOS by immunohistochemistry

Cited by 123 publications

References 41 publications

STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK− ALCL

STAT3 Mutation Is Associated with STAT3 Activation in CD30+ ALK− ALCL

Non-mycosis fungoides cutaneous lymphomas in a referral center in Taiwan: A retrospective case series and literature review

Cancer Classification at the Crossroads

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