RESUMO
Inflammatory Bowel Diseases (IBD) and intestinal tuberculosis (ITB) frequently share similar clinical, radiological, endoscopic and histologic features. The misdiagnosis of IBD can lead to worsening of ITB course, eventually with dissemination of Mycobacterium tuberculosis (MTB) due to immunosuppressive treatment. We herein report a challenging diagnosis of ITB, progressed from localized to disseminated, in a pregnant woman previously misdiagnosed with Crohn' disease (CD) on prolonged steroid treatment. Furthermore, we focus on three main issues: 1) the need for tuberculosis (TB) screening in pregnant women and in patients coming from TB endemic countries; 2) the effect of prolonged steroid treatment in misdiagnosed TB, particularly on its histological pattern; 3) the optimum clinical management of ITB.
Assuntos
Doença de Crohn , Mycobacterium tuberculosis , Tuberculose Gastrointestinal , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Gravidez , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/tratamento farmacológicoRESUMO
The prognostic value of Toll-like receptor 3 (TLR3) is debated in cancer, differing between tumor types, methods, and cell types. We recently showed for the first time that TLR3 expression on early stage non-small-cell lung cancer (NSCLC) results associated with a good prognosis. Here, we provide experimental evidences explaining the molecular reason behind TLR3's favorable prognostic role. We demonstrated that TLR3 activation in vitro induces apoptosis in lung cancer cell lines and, accordingly, that TLR3 expression is associated with caspase-3 activation in adenocarcinoma NSCLC specimens, both evaluated by immunohistochemistry. Moreover, we showed that TLR3 expression on cancer cells contributes to activate the CD103+ lung dendritic cell subset, that is specifically associated with processing of antigens derived from apoptotic cells and their presentation to CD8+ T lymphocytes. These findings point to the relevant role of TLR3 expression on lung cancer cells and support the use of TLR3 agonists in NSCLC patients to re-activate local innate immune response.
Assuntos
Apoptose/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias Pulmonares/imunologia , Proteínas de Neoplasias/imunologia , Receptor 3 Toll-Like/imunologia , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Caspase 3/imunologia , Linhagem Celular Tumoral , Humanos , Imunidade Inata , Imunoterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Camundongos , Receptor 3 Toll-Like/agonistasRESUMO
Immune and epithelial cells express TLR3, a receptor deputed to respond to microbial signals activating the immune response. The prognostic value of TLR3 in cancer is debated and no data are currently available in NSCLC, for which therapeutic approaches that target the immune system are providing encouraging results. Dissecting the lung immune microenvironment could provide new prognostic markers, especially for early stage NSCLC for which surgery is the only treatment option. In this study we investigated the expression and the prognostic value of TLR3 on both tumor and immune compartments of stage I NSCLCs. In a cohort of 194 NSCLC stage I, TLR3 immunohistochemistry expression on tumor cells predicted a favorable outcome of early stage NSCLC, whereas on the immune cells infiltrating the tumor stroma, TLR3 expression associated with a poor overall survival. Patients with TLR3-positive immune infiltrating cells, but not tumor cells showed a worse prognosis compared with all other patients. The majority of TLR3-expressing immune cells resulted to be macrophages and TLR3 expression associates with PD-1 expression. TLR3 has an opposite prognostic significance when expressed on tumor or immune cells in early stage NCSCL. Analysis of TLR3 in tumor and immune cells can help in identifying high risk stage I patients for which adjuvant treatment would be beneficial.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Receptor 3 Toll-Like/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor 3 Toll-Like/análiseRESUMO
OBJECTIVE: To analyze a procedure for breast cancer that requires performance of a molecular test before extensive intraoperative examination, fine needle aspiration cytology (FNAC) of surgically removed sentinel lymph nodes (SLNs). STUDY DESIGN: The diagnostic accuracy of extensive histologic examination and immunohistochemistry (IHC) of 101 SLNs from 98 breast carcinoma patients were compared with that of the evaluation of 2 specific mRNA markers by reverse transcriptase polymerase change reaction (mammaglobin and MUC-1). Cell specimens were obtained by FNAC of the SLNs immediately before freezing. RESULTS: Metastases were detected on frozen sections in 19 cases (18.81%). IHC on serial sections confirmed the metastases and showed micrometastases or isolated tumor cells in 24 SLNs (23.76%). Mammaglobin was expressed in 20 FNAC specimens (19.80%). MUC-1 assay was positive in 11 cases only (10.89%). CONCLUSION: This technique allows a complete histologic examination without sacrifice of part of the SLN and at the same time is a valuable diagnostic adjunct to the detection of occult tumor cells. Moreover, it is less expensive and time consuming than extensive IHC.