Abstract

Differentiation between adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is often challenging based on pathological findings alone. Although serum anti-HTLV-1 antibody positivity is required for ATLL diagnosis, this information is often not available at the time of pathological diagnosis. Therefore, we examined whether the expression of SOX4 and p16 would be helpful for differentiating the two disease entities. We immunohistochemically examined SOX4 and p16 expression (which have been implicated in ATLL carcinogenesis) in 11 ATLL patients and 20 PTCL-NOS patients and classified them into four stages according to the percentage of positive cells. Among the ATLL cases, 8/11 (73%) were SOX4-positive, while only 2/20 (10%) PTCL-NOS cases expressed SOX4. The mean total score was 4.2 (standard deviation (SD): 0.61) in the ATLL group and 0.50 (SD: 0.46) in the PTCL-NOS group (p < 0.001). Positive expression of p16 was noted in 4/11 (36%) patients with ATLL and 3/20 (15%) patients with PTCL-NOS, with mean total scores of 1.9 (SD: 0.64) and 0.70 (SD: 0.48) in the ATLL and PTCL-NOS groups, respectively (p = 0.141). These results suggest that SOX4 may be strongly expressed in ATLL compared to PTCL-NOS cases. Therefore, it may be helpful to perform immunohistochemical staining of SOX4 when pathologists face challenges discriminating between ATLL and PTCL-NOS.

Highlights

  • Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm that is typically composed of highly pleomorphic lymphoid cells [1]

  • We examined whether immunohistochemical determination of SRY-box transcription factor 4 (SOX4) and p16 expression may be useful for pathological differentiation of adult T-cell leukemia/lymphoma (ATLL) and PTCL-NOS

  • This study used immunohistochemical analysis of SOX4 and p16 expression in pa-. This used immunohistochemical of SOX4 expression in tients study with ATLL

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Summary

Introduction

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm that is typically composed of highly pleomorphic lymphoid cells [1]. PTCL-NOS is an aggressive lymphoma requiring combination chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), which was shown to be an improvement on the currently used treatment regimen in a recent clinical trial [8]. The human CDKN2A gene encodes a tumor suppressor protein known as p16 This cyclin-dependent kinase inhibitor regulates the G1 phase of the cell cycle and it is frequently inactivated in cancer [14]. SOX4 regulates transcription through numerous methods, mediating both gene activation and repression [15] This transcriptional regulator is known to form a complex with other proteins and plays a functional role in the apoptosis pathway, leading to cell death and tumor formation. SOX4 plays crucial roles in embryonic development [19], including the developmental processes that give rise to T-cells and B-cells [11]

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