RESUMEN
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare tumor linked to a dismal prognosis. Even the most effective chemotherapeutical regime of pemetrexed combined with cisplatin leads to a remission-rate of only about 40%. The reasons for the rather poor efficacy remain largely unknown. RESULTS: Phenotypes were significantly associated with progression (p=0.0279) and remission (p=0.0262). Cox-regression revealed significant associations between SLC19A1/TYMS-ratio (p=0.0076) as well as FPGS/TYMS-ratio (p=0.0026) and OS. For differentiation by risk-groups, COXPH identified a strong correlation (p=0.0008). METHODS: 56 MPM specimens from patients treated with pemetrexed were used for qPCR analysis. Phenotypes and risk groups were defined by their expression levels of members of the folic acid metabolism and correlated to survival and objective response. CONCLUSION: Our results indicate that the balance between folic acid uptake, activation and metabolism plays a crucial role in response to pemetrexed-based chemotherapy and the prognosis of MPM patients. Implementing this marker profile in MPM stratification may help to individualize MPM-therapy more efficiently.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Ácido Fólico/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Mesotelioma/genética , Mesotelioma/metabolismo , Mesotelioma Maligno , Persona de Mediana Edad , Pemetrexed/administración & dosificación , Péptido Sintasas/genética , Péptido Sintasas/metabolismo , Fenotipo , Neoplasias Pleurales/genética , Neoplasias Pleurales/metabolismo , Pronóstico , Proteína Portadora de Folato Reducido/genética , Proteína Portadora de Folato Reducido/metabolismo , Timidilato Sintasa/genética , Timidilato Sintasa/metabolismo , Resultado del TratamientoRESUMEN
We present a case of a histiocytic sarcoma incidentally detected in peripheral lung tissue resected for a spontaneous pneumothorax. Furthermore, we discuss the practical approach to pulmonary Langerhans cell histiocytosis, the main differential diagnosis of this lesion in the lung, based on morphological and immunohistochemical features. A 23-year-old male patient presented with recurrent pneumothoraces. The pulmonary tissue showed a single round granuloma-like lesion measuring 4 mm in diameter in close neighbourhood to a bronchial wall. The granuloma consisted of histiocytic cells with enlarged pale nuclei, plasma cells, lymphocytes and scanty eosinophilic granulocytes giving the impression of a granuloma of pulmonary Langerhans cell histiocytosis on haematoxylin and eosin (H&E) stains. Immunohistochemically, the histiocytic cells were negative for CD1a and S-100. They were positive for CD68, HLA-DR, CD14, CD4, CD11c, CD45LCA and lysozyme. MIB1 (Ki67) showed a nuclear staining of approximately 10% of the histiocytic cells. In summary, these findings were in keeping with a histiocytic sarcoma, a rare haematopoetic neoplasm. By demonstrating this particular case, we emphasise the importance of proving the diagnosis of pulmonary Langerhans cell histiocytosis by means of immunohistochemistry. In case of a negative CD1a reaction in a histiocytic lesion, further immunohistochemical studies have to be performed in order not to misdiagnose a malignant haematopoetic lesion.
Asunto(s)
Sarcoma Histiocítico/diagnóstico , Histiocitosis de Células de Langerhans/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neumotórax/diagnóstico , Diagnóstico Diferencial , Sarcoma Histiocítico/complicaciones , Sarcoma Histiocítico/patología , Histiocitosis de Células de Langerhans/patología , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Masculino , Neumotórax/etiología , Neumotórax/patología , Adulto JovenRESUMEN
With the appearance of defect-targeted therapies, the definition of tumour protein expression profiles has gained increasing importance. Two lung carcinoma tissue microarrays, one including 75 primary adenocarcinomas (ACs) and the other comprising 67 primary squamous cell carcinomas (SQCCs), were generated in the present study. On both arrays, each tumour was represented by an average of five cores. In addition, one punch of normal lung parenchyma adjacent to each tumour was included in the array. Immunohistochemical expression of 86 proteins was evaluated and the results were analysed by non-parametric tests, hierarchical clustering, and principal component analysis. In both tumour entities, parenchyma and tumours were clearly separated by hierarchical clustering. By the same statistical approach, it was possible to distinguish ACs from SQCCs with 98% accuracy and to distinguish parenchyma adjacent to ACs from that adjacent to SQCCs with 96% accuracy. It was also possible to separate ACs into three groups that significantly differed in survival. Cathepsin E and hsp105 were identified as previously unknown predictors of survival in lung AC. In summary, this study has shown that protein profiles are feasible tools for anticipating biological behaviour.