Mycosis Fungoide: Immunochemistry Analysis of Lymphoid and Microenvironment Cells by Macrotissue Array.

Aims: Cutaneous lymphomas (CL) represent a unique group of lymphomas and are the second most frequent extranodal lymphomas. CL probably is the result of a multifactor and multistep process. Firstly an inflammatory reactive process is developing secondary to various chronic stimuli that may be genetic, environmental, infectious and immunologic. The consequences are the negative effects in cell regulation and deregulation of oncogenes and/or suppressor genes later promotes transition from pre-neoplastic conditions to neoplasia. Detailed molecular expression analysis of cutaneous T-cell lymphoma is not available. Some oncogenic alterations have been demonstrated, such as functional inactivation of the Fas receptor, constitutive activity of STAT 3, or the inactivation of the p16 gene via deletion or promoter hypermethylation.

Objective: To study the expression of p16, c-myc, Ki67, bcl-2, CD1a, CD123, TCL1, CD68, STAT 3, STAT 4 and MAL1 in an homogeneous group of. CL diagnosed in a general Hospital in order to know more about the expression of these markers in this neoplastic process.

Design: retrospective, analytical study in 30 CL diagnosed consecutively as Mycosis Fungoide (14 early and 16 advanced stages) since January 2005 to December 2006. A macrotissue array technique by incubation with monoclonal antibodies and immunohistochemistry protocol to visualize by avidin-biotin peroxidases was applied in all paraffin histological samples. A semi quantitative method was applied in order to categorize the positive cells.

Results: In 28 samples (92%) we have observed p16 positive over expression, the two negative samples corresponding to early affectation. In 14 samples from early stages (48%) c-myc was negative. In 29 samples (96%) CD1a was positive in dermal and epidermal layer. CD123 (interleukine 3 receptor) was negative in 16 samples (52%) and TCL1 was positive in 12 cases (39%) in small cells with oval and cleaved nucleus and scarce cytoplasm. STAT3 and STAT4 were positive in 29 cases (97%), Over expression of MAL1 (48%) was observed in advanced patients with aggressive CL.

Conclusions: In our study an over expression of p16 is observed in the majority of cases and high c-myc expression in advanced stages. Probably dendritic plasmacytic cells are involved in the pathogenesis of skin lymphoproliferative disorders with cutaneous T cell infiltration. MAL1 could be a predictor of aggressive CL but it is necessary more studies and more cases in order to confirm it.