[ca] Fonament: La citologia del líquid pleural (LP) és poc sensible i té dificultats per diferenciar entre mesotelioma maligne (MPM) i adenocarcinoma (ADC) pulmonar o limfoma de tuberculosi (TBC). Objectiu: Descobrir "perfils proteòmics" al LP capaços de diferenciar aquestes entitats. Material i mètodes: Utilitzarem una micromatriu amb 120 biomarcadors proteics relacionats amb tumors sobre mostres de LP de 70 pacients (29 MPM, 29 ADC pulmonar i 12 limfomes amb ADA pleural elevada). L'abundància relativa dels biomarcadors comparada amb 35 subjectes amb DP secundari a TBC ens va permetre establir una empremta molecular per a les diferents etiologies. Els resultats van ser validats mitjançant tècniques d'ELISA en una cohort independent de 102 pacients. Resultats: La combinació de 4 proteïnes (proteïna C reactiva, metaloproteinasa-9, condroïtina sulfat i catepsina B) va distingir entre vessaments pleurals malignes (ADC o MPM) i benignes (TBC) amb una sensibilitat del 94,9% i el especificitat 84,7%. En la validació, van aconseguir una sensibilitat del 95% i especificitat del 100% per identificar DP malignes. Entre MPM d'ADC, la combinació de 4 proteïnes (CA15.3, CA19.9, kalikreína 12 i MMP-3) va obtenir una sensibilitat del 82,8% i una especificitat del 89,7%. En la validació un score amb la CA19.9, kalikreína 12 i CA15.3 va aconseguir una sensibilitat del 65% i especificitat del 100%. La catepsina B, en la cohort inicial, va discriminar entre DP secundari a limfomes i TBC amb una sensibilitat del 100% i especificitat del 83,3%. En el grup de validació, obté baixa especificitat (62%) malgrat la seva alta sensibilitat (95%). Conclusions: Un perfil proteòmic diferencia DPM de benigne i MPM de ADC mitjançant tècniques de ELISA. La catepsina B no discrimina la TBC del limfoma de manera eficaç.

[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.