[en] Background: Pleural fluid cytology has a limited sensitivity and the differentiation between adenocarcinoma (ADC) or mesothelioma (MPM) and tuberculosis (TBC) or lymphoma could be complicated. Objectives: Detect protein profiles in pleural fluids to differentiate: 1) benign from malignant pleural effusion 2) mesothelioma from lung ADC; 3) lymphoma with high pleural fluid ADA levels from TBC. Methodology: We performed a high-density, single-capture array of protein biomarkers related to cancer on stored pleural fluid supernatants from 70 patients (29 MPM, 29 lung ADC and 12 lymphoma with high pleural ADA activity). The relative abundance of the 120 biomarkers between these samples and those from 35 patients with pleural tuberculosis (paired controls) enabled to pattern the molecular signature of the different etiologic groups. The data obtained were subsequently validated in an independent cohort. Results: 1) Between benign and malignant pleural effusion, a combination of 4 proteins (C-reactive protein, MMP-9, CS and Cathepsin B) had a sensitivity of 94.9% and a specificity of 84.7%. The results were validated by ELISA obtaining a score with the combination of the 4 proteins that reached 95% of sensitivity and 100% of specificity. 2) Between MPM and ADC, a combination of 4 proteins (CA15.3, CA19.9, kallikrein 12 and MMP-3) demonstrated a sensitivity of 82.8% and a specificity of 89.7%. In the validation cohort, we obtained a score that combined CA19.9, kallikrein and CA15.3 and had a sensitivity of 65% and a specificity of 100%. 3) Cathepsin B, in the derivation cohort was able to discriminate between pleural effusion secondary to lymphoma with high ADA levels from TBC, with a sensitivity of 100% and a specificity of 83.3%. In the validation cohort, cathepsin B obtained a sensitivity of 62% and a specificity of 95%. Conclusions: A combination of 4 proteins or 3 proteins are useful to identify malignant pleural effusion vs benign and mesothelioma vs ADC, respective. Cathepsin B is not effective marker between TBC and lymphoma.

[es] Fundamento: La citología del líquido pleural (LP) es poco sensible y tiene dificultades para diferenciar entre mesotelioma maligno (MPM) y adenocarcinoma (ADC) pulmonar o linfoma de tuberculosis (TBC). Objetivo: Descubrir "perfiles proteómicos" en el LP que diferencien dichas entidades. Material y métodos: Utilizamos una micromatriz con 120 biomarcadores proteínicos relacionados con tumores sobre muestras de LP de 70 pacientes (29 MPM, 29 ADC y 12 linfomas con ADA pleural elevada). La abundancia relativa de los biomarcadores comparada con 35 sujetos con DP secundario a TBC nos permitió establecer una huella molecular para las diferentes etiologías. Validamos los resultados mediante técnicas de ELISA en una cohorte independiente de 102 pacientes. Resultados: La combinación de 4 proteínas (proteína C reactiva (PCR), MMP-9, condroitín sulfato y catepsina B) distinguió entre derrames pleurales malignos y benignos (TBC) con una sensibilidad del 94,9% y especificidad 84,7%. En la validación, alcanzaron una sensibilidad del 95% y especificidad del 100%. Entre MPM y ADC, la combinación de 4 proteínas (CA15.3, CA19.9, kalikreína 12 y MMP-3) obtuvo una sensibilidad del 82,8% y una especificidad del 89,7%. En la validación un score que incluyó el CA19.9, kalikreína 12 y CA15.3 alcanzó una sensibilidad del 65% y especificidad del 100%. La catepsina B, en la cohorte inicial, discriminó entre DP secundario a linfomas y TBC con sensibilidad del 100% y especificidad del 83,3%. En el grupo de validación, esta proteína obtuvo una baja especificidad (62%) a pesar de su alta sensibilidad (95%). Conclusiones: Un perfil proteómico diferencia DPM de benigno y MPM de ADC mediante técnicas de ELISA. La catepsina B no discrimina la TBC del linfoma de manera eficaz.