TOX Expression in Mycosis Fungoides and Sezary Syndrome

Abstract

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.

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

“…[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.…”

“…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.…”

The Value of Immunohistochemical Expression of TOX, ICOS, and GATA-3 in the Diagnosis of Mycosis Fungoides

“…(i) Negative: no staining, (ii) +1 (mild): <10%, (iii) +2 (moderate): 10% to 30%, (iv) +3 (strong): >30% 14…”

“…(i) Negative: no staining, (ii) +1 (mild): <10%, (iii) +2 (moderate): 10% to 30%, (iv) +3 (strong): > 30%. 14 ICOS cytoplasmic expression in epidermal exocytotic lymphocytes and/or dermal lymphocyte was evaluated as 0 = no staining, low expression = 5%, moderate expression = 5% to 50%, high expression = > 50% of cells stained positive. 7 GATA-3 nuclear expression intensity in epidermal exocytotic lymphocytes and/or dermal lymphocyte was evaluated as (no staining = 0, mild staining = 1, moderate staining = 2, strong staining = 3).…”