Immunohistochemical Expression Patterns of CD45RO, p105/p50, JAK3, TOX, and IL-17 in Early-Stage Mycosis Fungoides

Aladily, Tariq N.; Abushunar, Tasnim; Alhesa, Ahmad; Alrawi, Raneen; Almaani, Noor; Abdaljaleel, Maram

doi:10.3390/diagnostics12010220

Cited by 5 publications

(9 citation statements)

References 26 publications

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“…[12][13][14][15] However, TOX expression has been recently reported to be not specific to neoplastic T lymphocytes but also seen in reactive lymphocytes found in BIDs. [44][45][46] Consistent with the studies that challenged the original reports, TOX expression was observed in both MF and BIDs, and TOX seemed to have no diagnostic value for eMF. ) and is involved in the differentiation of naive T cells into Th1.…”

Section: Discussionsupporting

confidence: 77%

“…The original and subsequent several studies showed that TOX expression was significantly increased in eMF, whereas it was negative or weakly increased in BIDs, and TOX was proposed as a diagnostic marker for eMF 12–15 . However, TOX expression has been recently reported to be not specific to neoplastic T lymphocytes but also seen in reactive lymphocytes found in BIDs 44–46 . Consistent with the studies that challenged the original reports, TOX expression was observed in both MF and BIDs, and TOX seemed to have no diagnostic value for eMF.…”

Section: Discussionmentioning

confidence: 84%

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TOX, TWIST1, STAT4, and SATB1 protein expressions in early‐stage mycosis fungoides

Örnek,

Ozekinci,

Ipin

et al. 2023

J Cutan Pathol

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BackgroundDiagnosis of early mycosis fungoides (eMF) is challenging and often delayed as many of its clinical and histopathologic features may mimic various benign inflammatory dermatoses (BIDs). The products of the thymocyte selection‐associated high mobility group box (TOX), twist family BHLH transcription factor 1 (TWIST1), signal transducer and activator of transcription 4 (STAT4), and special AT‐rich sequence‐binding protein 1 (SATB1) genes function as transcription factors and are involved in the pathogenesis of MF.ObjectivesWe aim to determine the diagnostic value of TOX, TWIST1, STAT4, and SATB1 protein expressions in eMF.MethodsThis non‐randomized, controlled, prospective analytic study was conducted by performing immunohistochemistry staining with TOX, TWIST1, STAT4, and SATB1 polyclonal antibodies in lesional skin biopsies of eMF and BID patients. Nuclear staining of lymphocytes was compared between eMF and BIDs, and the capacity of these antibodies to predict eMF was determined.ResultsImmunostainings with anti‐TWIST1 showed an increase in protein expression (p = 0.003) and showed a decrease with anti‐SATB1 antibodies in eMF compared to BIDs (p = 0.005) while anti‐TOX and anti‐STAT4 antibodies did not exhibit significant differences (p = 0.384; p = 0.150). Receiver operating characteristic analysis showed that immunohistochemical evaluations of TWIST1 and SATB1 protein expressions can differentiate eMF (area under the curve [AUC]: 0.728, 95% confidence interval [CI]: 0.605–0.851, p = 0.002; AUC: 0.686, 95% CI: 0.565–0.807, p = 0.013).ConclusionsTWIST1 and SATB1 are potential diagnostic markers for the histologic diagnosis of eMF.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 84%

TOX, TWIST1, STAT4, and SATB1 protein expressions in early‐stage mycosis fungoides

Örnek,

Ozekinci,

Ipin

et al. 2023

J Cutan Pathol

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“…It has been hypothesised that TOX may promote the formation of exhausted T-cells akin to what happens after the stimulation of immune checkpoints such as PD-1 or CTLA-4 [ 38 , 39 ]; and it may play a role in cancer pathogenesis and progression. Some studies have evaluated TOX role in MF/SS providing contrasting results on its potential role as a diagnostic and prognostic marker [ 31 , 32 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. The present study aims to evaluate TOX role of in MF/SS as a possible diagnostic marker by comparing its expression in MF/SS and in inflammatory skin diseases, and to assess whether TOX may also have a prognostic role.…”

Section: Introductionmentioning

confidence: 99%

TOX Expression in Mycosis Fungoides and Sezary Syndrome

et al. 2022

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Mycosis fungoides (MF) and Sezary syndrome (SS) are the two most common type of cutaneous T-cell lymphoma (CTCL). Currently, no markers can be clearly related to prognosis or to differential diagnosis between early stages and inflammatory benign diseases (IBD). The thymocyte selection-associated high mobility group box factor (TOX), has been proposed as a possible marker in differential diagnosis between early CTCL stages and IBD. Recently TOX has been related to prognosis. We aimed to investigate whether TOX may be a diagnostic or prognostic marker. MF and SS biopsies between 2010 and 2020 were retrieved. New tissues slides were stained with an anti-TOX antibody, (Clone NAN448B). On each slide, 5 fields were examined at high magnification (400×), to evaluate the percentage of marker-positivity in a quantitative way. Thirty-six patients (12 females and 24 males) and 48 biopsies were collected. Nine patients had multiple biopsies. TOX expression in MF/SS cases showed an increase from early to advanced phases. TOX was not regarded as a prognostic marker due to the absence of significant changes by comparing early MF cases with reactive conditions. TOX statistical significance increased in patients alive with disease and in those dead of disease (p = 0.013 and = 0.0005, respectively) as compared with patients in complete remission. Our results show that TOX should be regarded more as a prognostic than a diagnostic marker.

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“…In 2012, for the first time, TOX was reported to discriminate between early MF lesions and biopsies from BID 7 , however, this has not been confirmed by some later studies 8 . Other reports revealed that TOX was also expressed in infiltrating lymphocytes in BID, although the frequency of positive cells was not as high as in MF.…”

Section: Thymocyte Selection Associated High Mobility Group Box (Tox)mentioning

confidence: 91%

Novel Biomarkers in Cutaneous T Cell Lymphomas

Przybylski¹

2022

Preprint

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Cutaneous T cell lymphomas (CTCLs) are caused by malignant clonal proliferation of skin-tropic T cells. Most patients have an indolent disease course managed with skin-directed therapies, while some entities, or in advanced stages of disease, have aggressive progression and poor survival. To efficiently treat CTCL consistent entity markers are needed to prevent the delay in diagnosis and to provide disease specific treatment to patients. Recently, the introduction of high throughput parallel sequencing methods resulted in identification of numerous genetic and ep-igenetic alterations affecting the transcriptome of CTCL cells. In this review, most relevant genes, including TOX, CADM1, PLS3, DNM3, CXCL13, PD-1, BCL11B and TMEM244 are reported that are specifically expressed in CTCL. Upon verification their specificity and sensitivity in larger studies, their altered expression will be able to be recognized as novel biomarkers, that can im-prove the early diagnosis of CTCL.

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Immunohistochemical Expression Patterns of CD45RO, p105/p50, JAK3, TOX, and IL-17 in Early-Stage Mycosis Fungoides

Cited by 5 publications

References 26 publications

TOX, TWIST1, STAT4, and SATB1 protein expressions in early‐stage mycosis fungoides

TOX, TWIST1, STAT4, and SATB1 protein expressions in early‐stage mycosis fungoides

TOX Expression in Mycosis Fungoides and Sezary Syndrome

Novel Biomarkers in Cutaneous T Cell Lymphomas

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