ABSTRACT
Patients with NTRK-rearranged tumors can be now treated using anti-TRK-targeted therapies making NTRK testing important for treatment choices in patients with advanced cancers. Pan-TRK immunohistochemistry (IHC) could be a valuable premolecular screening strategy in this field. The choice of 1 IHC method or another requires to investigate for intermethod comparison. A high frequency of pan-TRK positive tumors among salivary gland tumors makes these tumors particularly appropriate for such a technical study. In this work, we studied the intermethod agreement for 2 pan-TRK IHC methods (using A7H6R and EPR17341 clones) in a file of salivary gland tumors of different subtypes. Among 71 tumors, pan-TRK IHC was diagnosed as positive (ie, H score ≥5) in 23 and 18 cases using EPR17341 and A7H6R clones, respectively, with a good intermethod agreement in terms of positive/negative result (κ, 0.70) but only a moderate agreement considering the H score values themselves (intraclass correlation coefficient of 0.5399). Beyond the intensity of staining and the percentages of stained cells, major differences were also observed between the location and type of cells stained in positive cases between the 2 clones. The single NTRK-rearranged case in our series (ie, a NTRK3-rearranged salivary secretory carcinoma) was positive with the 2 pan-TRK antibodies. Future studies including molecularly proven NTRK-rearranged tumors remain required to further study and compare the performances of different pan-TRK clones in the screening of NTRK-rearranged cancers but it is now obvious that the staining patterns of A7H6R and EPR17341 clones are not strictly identical.
Subject(s)
Biomarkers, Tumor/metabolism , Immunohistochemistry/methods , Receptor, trkA/metabolism , Salivary Gland Neoplasms/metabolism , Salivary Glands/metabolism , Adult , Aged , Antibodies/metabolism , Clone Cells , Female , Humans , Male , Middle Aged , Receptor, trkA/immunology , Salivary Gland Neoplasms/diagnosis , Salivary Gland Neoplasms/pathology , Salivary Glands/pathology , Staining and Labeling , Young AdultABSTRACT
Beyond targeted therapy for patients with BRAF-mutated melanomas and immunotherapy in patients lacking BRAF mutations, anti-MEK therapy has been proposed in patients with advanced melanomas harbouring BRAF fusions. BRAF fusions diagnosis in patients with advanced melanomas is the subject of the present study. Using BRAF fluorescent in situ hybridisation (FISH), we searched for BRAF fusions in 74 samples of 66 patients with advanced BRAF/NRAS/KIT wild-type melanomas. We identified 2/66 (3%) patients with BRAF fusions in a brain metastasis of one patient and in a lymph node metastasis and in a cutaneous metastasis for the second patient with 90%-95% of tumour nuclei containing isolated 3'-BRAF FISH signals. As a result, we conclude that BRAF FISH in patients with advanced BRAF/NRAS/KIT wild-type melanomas is a valuable and easy-to-perform test to diagnose BRAF fusions and to identify patients who could benefit of anti-MEK targeted therapy.
Subject(s)
Biomarkers, Tumor/genetics , GTP Phosphohydrolases/genetics , Gene Fusion , In Situ Hybridization, Fluorescence , Melanoma/genetics , Membrane Proteins/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-kit/genetics , Skin Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Female , Humans , Male , Melanoma/drug therapy , Melanoma/enzymology , Middle Aged , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinase Kinases/metabolism , Molecular Targeted Therapy , Patient Selection , Precision Medicine , Predictive Value of Tests , Protein Kinase Inhibitors/therapeutic use , Skin Neoplasms/drug therapy , Skin Neoplasms/enzymologyABSTRACT
Leprosy is still a largely worldwide spread disease but rarely encountered in metropolitan France. Its identification implies a multidisciplinary clinical, pathological and bacteriological diagnosis which is necessary to an efficient antibiotic treatment against a crippling disease which remains curable. Here we report the case of a 24-year-old man who was showing an original both cutaneous and pulmonary presence of acido-alcooloresistant bacillus which have been identified as Mycobacterium leprae by polymerase chain reaction (PCR). This unusual presentation of a cutaneous and pulmonary leprosy raises the problem of its differential diagnoses, including those of non-tuberculosis mycobacterial infections.
