Revision of the fourth edition of the World Health Organisation (WHO) Classification of Haematopoietic and Lymphatic Tissues, which was published in 2017, introduced important changes updating the biology, pathology, genetics, and clinical presentation of aggressive B-cell lymphomas. High grade B-cell lymphomas (HG-BLs) replaced B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, the new provisional entityBurkitt-like lymphoma with 11q aberration was identified, and some categories were upgraded, e.g. EBV-positive diffuse large B-cell lymphoma, not otherwise specified. Still the histopathological diagnostics is based on morphology and immunoprofile, but to define the HGBLs evaluation of MYC, BCL2, and BCL6 gene statuses is required. According to the presented WHO criteria, in the comprehensive histopathological diagnostics of aggressive B-cell lymphomas a highly specialised diagnostic team including a pathologist, a molecular biologist, a geneticist, a haematologist, and immunophenotyping technicians is needed.
Expression of the multidrug resistance gene MDR1 is reported to be an important determinant of the response to chemotherapy and survival in some cancers. We compared three methods for determining the intrinsic MDR1 expression in soft tissue sarcomas. We studied MDR1 gene expression in 39 samples from 33 cases of soft tissue sarcomas comprising 11 liposarcomas, nine malignant fibrous histiocytomas, six leiomyosarcomas, four malignant schwannomas, three fibrosarcomas, three synovial sarcomas, and three epithelioid sarcomas, and seven cases of benign soft tissue tumors in adult patients. To detect MDR1 mRNA, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed in all samples. Furthermore, RNA dot-blot analysis with digoxigenin-labeled RNA probe and immunohistochemistry with JSB-1 and C-219 antibodies for P-glycoprotein were employed in 34 and 37 samples in soft tissue sarcomas, respectively. We compared these three detection techniques. Of the 39 specimens, 18 (46%) showed MDR1 PCR products. Liposarcomas (six of 11), malignant fibrous histiocytomas (six of nine), leiomyosarcomas (four of six), fibrosarcomas (two of three) revealed high or intermediate MDR1 expression at high frequency. No MDR1 expression was detectable in malignant schwannomas, synovial sarcomas, or epithelioid sarcomas. Of seven benign soft tissue tumors, one ganglioneuroma and one lipomatosis showed low levels of MDR1 expression. By RNA dot-blot analysis, MDR1 transcripts were detectable in 12 of 34 specimens (35%). Four samples were negative by dot blot despite positivity with RT-PCR. Concordance between MDR1 expression by RNA level with RT-PCR and dot blot and at the protein level with immunohistochemistry using C-219 was found in 16 (47%) of the 34 comparable specimens. Eight samples showed positive immunoreactivity for C-219 despite negative results in RT-PCR and dot-blot analysis. The intrinsic MDR1 expression in soft tissue sarcoma seemed to depend on certain tumor types, such as liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and fibrosarcoma. For the evaluation of MDR1 expression, RT-PCR is useful because of its relative simplicity and sensitivity. However, the clinical significance of such low levels of MDR1 expression detected only by RT-PCR must be discussed within systematically treated patient groups.
Background and Objectives:Radical surgery is the best mode of treatment of retroperitoneal sarcomas (RS); however, common recurrences are unpredictable. Methods: For the better understanding of outcomes and possibilities of treatment retrospective analysis of different factors, including DNA content, was performed based on 70 patients. Results: Leiomyosarcoma and liposarcoma were most common histologic types of classified sarcomas. Different kinds of resection were successfully performed in 51 patients (73%) and 35 of their available DNA specimens were analyzed. The actuarial 5-and 10-year survival rates in the resection group were 53% and 40%, respectively, with the median survival of 57 months. Patients with diploid resected tumors had a better 10-year survival rate (58%), than those patients with aneuploid tumors (25%,)-P < 0.005. Those patients with low-grade sarcomas had a significantly longer survival than those with high-grade sarcomas (10-year survival rate: 44% compared to 29%). In the univariate analysis, adjuvant therapy, type of histology, type of surgery, location of tumor, and S-phase fraction had no influence on survival. In the multivariate analysis (Cox), only ploidy was an independent prognostic variable. Relative risk of death was over three times higher for aneuploid than for diploid tumors. Conclusion: Tumor ploidy should be analyzed in every case of retroperitoneal sarcoma for better assessment of prognosis and possible indication for adjuvant therapy.
We examined the mRNA expression of the multidrug- resistance-associated protein gene (MRP) in soft-tissue sarcomas and compared it with the expression of the multidrug resistance gene (MDR1), using the reverse transcriptase/polymerase chain reaction. We investigate 39 samples from 33 cases of soft-tissue sarcomas (11 liposarcomas, 9 malignant fibrous histiocytomas, 6 leiomyosarcomas, 4 malignant schwannomas, 3 fibrosarcomas, 3 synovial sarcomas, and 3 epithelioid sarcomas) and 7 benign soft-tissue tumors. All samples were obtained prior to chemotherapy. An expression of MRP mRNA was noted in 56% of soft-tissue sarcoma specimens. The co-expression of MRP and MDR1 was recognized in 15 samples (38%) (5/11 liposarcomas, 5/9 malignant fibrous histiocytomas, 3/6 leiomyosarcomas, 2/3 fibrosarcomas) and significantly correlated with histological grade (P=0.0165). A positive and significant correlation was found between MRP and MDR1 expression in soft-tissue sarcomas(P=0.0013). In benign soft-tissue tumors, 1 chemodectoma and 1 neurothekeoma showed low MRP expression; however, no case showed co-expression of MRP and MDR1.
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