Advanced-stage mycosis fungoides: role of the signal transducer and activator of transcription 3, nuclear factor-κB and nuclear factor of activated T cells pathways.

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.

Implementación de un sistema de calidad en la Red Nacional de Bancos de Tumores del Centro Nacional de Investigaciones Oncológicas / Implementation of a quality assurance programme in the spanish national tumour bank network promoted by the Spanish National Cancer Center

Los Bancos de Tumores son una pieza fundamental en la oncología actual, tanto en investigación como en asistencia. Su actividad se define en base a una serie de protocolos hospitalarios que permiten el estudio molecular de grandes series de neoplasias, de forma que su más eficaz diseño es el trabajo en red cooperativa. Las políticas de control de calidad son una parte esencial de los servicios, públicos o privados, basados en plataformas tecnológicas. En este sentido, la investigación biosanitaria y la asistencia clínica debería desarrollar progresivamente sistemas de gestión de calidad que minimicen el riesgo de errores derivados de la ausencia de protocolización de sus actividades, el riesgo de errores derivados del uso inapropiado de tecnología y, por ultimo, localizar y solucionar problemas relacionados con la calidad final. El presente artículo presenta las bases del programa de garantía de calidad puesto en marcha por la Red Nacional de Bancos de Tumores promovida por el CNIO, una plataforma cooperativa que agrupa a algunos de los principales hospitales españoles

Tumour banks are a centrepiece in current oncological research and assistance. Their activity is defined by a series of hospital protocols that allow molecular studies of tumour samples, and networking appears to be the best environment for tumour banks to grow in. Public and private service sectors must include quality control policies, especially if they are related to technological platforms. In this sense, bio-sanitary research support or welfare services, should progressively develop quality control systems that minimize errors derived from the lack of protocol; they should minimize errors derived from the incorrect use of technology and equipments; and finally, they should find and solve weak points in terms of final quality. The following article presents the quality assurance policy basis of the Spanish National Tumour Bank Network promoted by The Spanish National Cancer Centre (CNIO), a cooperative platform formed by some of the main Spanish hospitals

[T-lymphocyte subpopulations in acute viral hepatitis]. / Subpoblaciones de linfocitos T en hepatitis viral aguda.

The variability of the clinical course in viral hepatitis depends more on the immune response of the host that on the type of virus involved. Inductors/helpers (LT4) or cytotoxic/suppressors (LT8) T-lymphocytes regulate the immune response which can be modified during infection or in homosexuals who are at high risk for viral infection. We studied 45 males with viral hepatitis (25 B, 13 A, and 7 non A-non B hepatitis), 20 normal and 20 homosexual subjects. LT4, LT8 and B lymphocytes were determined by immunofluorescence in peripheral blood. A significant and transient decrease in levels of LT4 was found in A and B hepatitis (670 and 591 per ml vs 873 for normals). In some hepatitis B cases this decrease persisted until the HB serum antigen disappeared. Increased levels of LT8 were found in asymptomatic or hepatitis B infected homosexuals (682 and 782 respectively vs 506 per ml in normals). No difference from normals were found in non A-non B hepatitis. B lymphocytes were normal in all groups. Serum factors acting as immunoregulators of suppressors of LT4 function may be involved in the delayed synthesis of anti-HB serum antibody.