ABSTRACT
AIMS: (1) To validate a quantitative real time methylation specific PCR assay (MethyLight) for the detection of O6-methylguanine-DNA methyltransferase (MGMT) gene methylation status (MS) in diffuse large B-cell lymphoma (DLBCL). (2) To determine the immunohistochemical (IHC) expression of the MGMT protein and correlate it with MS. Both IHC and MethyLight results were compared with patient's outcome. METHODS: 71 patients with primary nodal DLBCL were studied. MGMT immunoreactivity was detected using a specific monoclonal antibody. The MS of MGMT gene was analysed in 52/71 DLBCL using MethyLight. A selected subset of 40 DLBCL was also analysed using qualitative methylation-specific PCR (MSP). Statistical analysis of overall survival (OS), lymphoma-specific survival (LSS) and progression free survival (PFS) was performed according to IHC and MS results. RESULTS: 19/71 DLBCLs (27%) were MGMT-negative at IHC; all were analysed, together with 33/52 MGMT-positive DLBCLs. MethyLight showed a better performance than MSP. There was a good correlation between the presence of MGMT expression and the unmethylated status; the absence of IHC expression was poorly correlated with the presence of methylation. Better OS, LSS and PFS was found in DLBCLs with MGMT gene methylation. DLBCLs not expressing MGMT at IHC showed a longer PFS. CONCLUSIONS: The quantitative real-time methylation-specific PCR assay for the detection of MGMT gene hypermethylation has been validated for the first time in DLBCL. Immunohistochemistry seems to represent an useful preliminary test to identify unmethylated cases; MS analysis may be performed in non-immunoreactive cases to identify truly methylated DLBCLs, which bear a better prognosis.
Subject(s)
Biomarkers, Tumor/genetics , DNA Methylation , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Tumor Suppressor Proteins/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Chromosomes, Human, Pair 10/genetics , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , DNA, Neoplasm/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasm Staging , Polymerase Chain Reaction/methods , Survival Analysis , Tumor Suppressor Proteins/metabolismABSTRACT
Proximal type epithelioid sarcoma is a rare neoplasia in which morphological findings are characterized by nodular proliferation of epithelioid cells with focal rhabdoid features. It shares some histological features with other neoplasias and this gives an account of several differential diagnosis with other extrarenal rhabdoid tumors. Immunohistochemical and ultrastructural analysis are important in defining this entity: vimentin, cytokeratin, EMA and often CD34 expression of tumoral cells, moreover ultrastructurally evidence of large paranuclear whorls of intermediate filaments, are requested for diagnosis. A correct diagnostic framing is necessary because of the aggressive clinical behaviour of this tumor, that has a tendency to early spreading. We describe a case of vulvar proximal type epithelioid sarcoma in a 34 years old woman.
Subject(s)
Diagnostic Errors , Sarcoma/diagnosis , Vulvar Neoplasms/diagnosis , Adult , Antigens, CD34/analysis , Biomarkers, Tumor/analysis , Diagnosis, Differential , Epidermal Cyst/diagnosis , Female , Humans , Intermediate Filaments/pathology , Lymph Node Excision , Mucin-1/analysis , Neoplasm Proteins/analysis , Reoperation , Rhabdoid Tumor/classification , Rhabdoid Tumor/diagnosis , Sarcoma/chemistry , Sarcoma/pathology , Sarcoma/surgery , Vulvar Neoplasms/chemistry , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgeryABSTRACT
The authors evaluate the clinical efficacy and tolerability of the new wide-spectrum fluoroquinolone ciprofloxacin for management of respiratory tract infections. Of the 20 patients enrolled and treated with 500 mg ciprofloxacin tablets twice daily, 17 (85%) were completely cured, and tolerance was excellent in 19 (95%).
