Contents lists available at ScienceDirect Pathology - Research and Practice journal homepage: www.elsevier.com/locate/prp Original article Potential predictive value of cofilin-1 for metastasis occurrence in a small cohort of Argentinian patients with mid-low Breslow thickness melanoma Irene L. Ibañez a,b, ⁎ , Francisco M. Grings b , Candelaria Bracalente b , Adriana R. Rinflerch c , Victoria Volonteri d , Mauro A.A. Castro e , Fabio Klamt f,g , Hebe Durán a,b,h a National Atomic Energy Commission, (CNEA), Constituyentes Atomic Center, Research, Applications Management, Av. General, B1650KNA, San Martín, Buenos Aires, Argentina b National Scientific and Technical Research Council (CONICET), C1425FQB, CABA, Argentina c Italian Hospital of Buenos Aires (HIBA), Department of Dermatology, Experimental Dermatology, C1199ABB, CABA, Argentina d Italian Hospital of Buenos Aires (HIBA), Department of Anatomic Pathology, C1199ABB, CABA, Argentina e Laboratory of Bioinformatics, Curitiba (PR), Federal University of Paraná (UFPR), Professional and Technological Education Sector, Polytechnic Center Laboratory of Bioinformatics and Systems Biology, PPG-Bioinformática Jardim das Américas, 81531-970, Curitiba, PR, Brazil f Federal University of Rio Grande do Sul (UFRGS), Institute of Basic Health Sciences (ICBS), Department of Biochemistry, Laboratory of Cellular Biochemistry, 90035- 003, Porto Alegre, RS, Brazil g National Institutes of Science & Technology, Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil h National University of San Martin, Miguelete Campus, School of Science and Technology, B1650KNA, Villa Lynch, Buenos Aires, Argentina ARTICLE INFO Keywords: Cofilin-1 Melanoma Metastasis Breslow thickness Bayesian analysis ABSTRACT Nowadays, histopathological criteria for melanocytic lesions are the mainstay prognostic factors for melanoma. However, there are cases in which these parameters fall short to predict melanoma spread. We recently demonstrated a correlation of cofilin-1 levels, a key protein for tumor invasion, with different histopathological parameters associated with melanoma malignancy as well as a negative correlation with survival. In order to broaden our previous findings, we aim to estimate the probability of a melanoma to me- tastasize as a function of both a conventional histopathological parameter (Breslow thickness, BT) and cofilin-1’s immunohistochemical expression levels, which we propose as a potential marker for metastasis. We used a Bayesian approach to analyze clinical and cofilin-1 datasets formerly obtained from a patients' small cohort diagnosed with malignant melanocytic lesions since 2000 until 2008; classified at different tumor stages with or without detected metastasis and with at least 5 years of clinical follow-up. Low BT values exhibited wide variance to predict metastasis occurrence, while the differential diagnostic value of cofilin-1 confirmed BT diagnosis or resulted more precise to predict outcome. Particularly, the prob- ability of metastasis estimation improved when cofilin-1 was combined with BT for specific cases, where BT displayed large uncertainties. Our analysis and the cofilin-1 determination provided statistically significant prognostic value in mid-low BT melanomas, which could complement further evaluation criteria to assist diagnosis and treatment decision- making. Moreover, the combined use of cofilin-1 with BT, if validated in follow-up studies, would be feasible to help patients’ selection for treatment and optimize health resources. https://doi.org/10.1016/j.prp.2019.152582 Received 28 June 2019; Received in revised form 26 July 2019; Accepted 3 August 2019 Abreviations: A.U., arbitrary units; BT, Breslow thickness; HIBA, Italian Hospital of Buenos Aires; IHC, immunohistochemical; MCMC, Markov chain Monte Carlo; met, metastasis; O.D., optical density; p, probability of metastasis; P(met| BT), probability of metastasis given BT; P(met |cofilin-1), probability of metastasis given cofilin-1; P(met| BT,cofilin-1), probability of metastasis given both BT and cofilin-1; PPPM, predictive, preventive and personalized medicine; TCGA, The Cancer Genome Atlas ⁎ Corresponding autor at: Comisión Nacional de Energía Atómica, Gerencia de Investigación y Aplicaciones, Av. General Paz 1499, B1650KNA, San Martín, Provincia de Buenos Aires, Argentina. E-mail addresses: irenuliz@yahoo.com (I.L. Ibañez), francisco.m.grings@gmail.com (F.M. Grings), candybraca@gmail.com (C. Bracalente), adriana.rinflerch@hospitalitaliano.org.ar (A.R. Rinflerch), victoria.volonteri@hospitalitaliano.org.ar (V. Volonteri), mauro.a.castro@gmail.com (M.A.A. Castro), 00025267@ufrgs.br (F. Klamt), hduran@cnea.gov.ar (H. Durán). Pathology - Research and Practice xxx (xxxx) xxxx 0344-0338/ © 2019 Elsevier GmbH. All rights reserved. Please cite this article as: Irene L. Ibañez, et al., Pathology - Research and Practice, https://doi.org/10.1016/j.prp.2019.152582