Cofilin-1 levels and intracellular localization are associated with melanoma prognosis in a cohort of patients.

Melanoma is an aggressive cancer with highly metastatic ability. We propose cofilin-1, a key protein in the regulation of actin dynamics and migration, as a prognostic marker. We determined cofilin-1 levels in a retrospective cohort of patients with melanomas and benign lesions of melanocytes (nevi) by immunohistochemistry. Higher cofilin-1 levels were found in malignant melanoma (MM) with Breslow Index (BI)>2 vs MM with BI<2, melanoma in situ (MIS) and nevi and also in MM with metastasis vs MM without detected metastasis. Kaplan-Meier survival curves were performed, clustering patients according to either the type of melanocytic lesions or cofilin-1 level. Survival curves demonstrated worse prognosis of patients with high vs low cofilin-1 levels. TCGA database analysis of melanoma also showed low survival in patients with upregulated cofilin-1 mRNA vs patients without alteration in CFL1 mRNA expression. As cofilin-1 has a dual function depending on its intracellular localization, we evaluated nuclear and cytoplasmic levels of cofilin-1 in melanoma and nevi samples by immunofluorescence. MM with high Breslow index and metastatic cells not only presented cytoplasmic cofilin-1, but also showed this protein at the nucleus. An increase in nuclear/cytoplasmic cofilin-1 mean fluorescence ratio was observed in MM with BI>2 vs MM with BI<2, MIS and nevi. In conclusion, an association of cofilin-1 levels with malignant features and an inverse correlation with survival were demonstrated. Moreover, this study suggests that not only the higher levels of cofilin-1, but also its nuclear localization can be proposed as marker of worse outcome of patients with melanoma.

Escleredema diabético: presentación de un caso y revisión de la literatura / Diabetic escleredema: presentation of a case and revision of literature

El escleredema es una entidad infrecuente de etiología desconocida, que se caracteriza por el engrosamiento de la piel del cuello, los hombros y la espalda. Generalmente se observa en pacientes diabéticos. Presentamos el caso de un varón de 74 años, diabético tipo II, que cursa internación en la unidad de cuidados intensivos por un accidente cerebro-vascular y neumonía grave. Al examen dermatológico presentaba una placa de escleredema en cuello, hombros y parte alta del dorso, sobre la que asentaba una úlcera provocada por el decúbito obligado.