Alterations of cell cycle regulators in localized synovial sarcoma: A multifactorial study with prognostic implications.
(1/48)
Genetic alterations of cell cycle regulators are thought to represent uncommon and possible secondary events in sarcomas characterized by recurrent chromosomal translocations. The present study investigates this hypothesis on synovial sarcoma (SS), assessing the frequency of expression and possible clinical implications of detecting alterations in critical cell cycle regulatory proteins. A homogeneous cohort of 49 patients with localized SS, restricted to the extremity and with available long-term follow-up information, was selected from our files. We focused our study on molecules involved in the G1 checkpoint and G1-S transition, including cyclins D1 and E, p21(WAF1), p27(Kip1), mdm2, p53, and Ki67. A cutoff point of 10% immunoreactive tumor cell nuclei was selected to define a positive phenotype for any given marker, except for Ki67. High Ki67 proliferative index was considered when >/=20% tumor cells displayed nuclear immunoreactivity. Biphasic SS were analyzed, taking into account separately the expression of these proteins in the spindle and glandular components. Disease specific survival was modeled using the Kaplan-Meier method with log rank test and Cox regression. The cohort of patients analyzed included 23 females and 26 males, and the histological type distribution was 35 monophasic and 14 biphasic SS. The median follow-up for survivors was 53 months, with a 5-year disease-specific survival of 63% and a metastatic disease-free survival of 40%. The positive phenotypes identified for the different markers studied were as follows: cyclin D1, 59%; cyclin E, 29%; p21, 51%; p27, 69%; mdm2, 59%; p53, 16%; and Ki67, 59%. We observed that positive p53, cyclin E, and high Ki67 proliferative index were correlated with survival, but only Ki67 and p53 were independent variables for prognostication. The present study suggests that alterations of cell cycle regulators are more common events in SS than originally thought. p53 overexpression could be of use as a marker together with a high Ki67 proliferative index, in identifying a subset of SS patients with increased risk of tumor relapse. (+info)
Three patients with lipoma arborescens of the knee joint were evaluated with high resolution ultrasonography. All patients demonstrated a hyperechoic, frondlike mass in the suprapatellar bursa with a large associated effusion. All had popliteal cyst formation without involvement by the mass. Dynamic compression and manipulation of the suprapatellar effusion demonstrated pliable and flexible nature of mass with bending and waving of the frondlike mass in real time. Comparison with MR imaging demonstrated similar extent, location, and morphology of the mass. The characteristic features of this lesion as well as its distribution in the knee joint can be demonstrated readily by sonography. (+info)
Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal.
(3/48)
It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype. (+info)
Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue.
(4/48)
A recombinant antibody-lymphotoxin-alpha fusion protein induced an adaptive immune response protecting mice from melanoma. Importantly, this fusion protein elicited the formation of a lymphoid-like tissue in the tumor microenvironment containing L-selectin+ T cells and MHC class II+ antigen-presenting cells, as well as B and T cell aggregates. Furthermore, PNAd+/TCA4+ high endothelial venules were observed within the tumor, suggesting entry channels for naive T cell infiltrates. Over the course of therapy, a marked clonal expansion of certain TCR specificities occurred among tumor-infiltrating lymphocytes that displayed reactivity against melanoma cells and the TRP-2(180-188) peptide. Consequently, naive T cells may have been recruited to as well as primed and expanded in the lymphoid-like tissue induced by the lymphotoxin-alpha fusion protein at the tumor site. (+info)
Granulocytic sarcoma of humerus, an unusual association of acute myeloblastic leukemia--a case report.
(5/48)
Ganulocytic sarcoma (Chloroma) is a tumour of rare variety usually in assocoiation with granulocytic leukemia. It is related to soft tissue with extramedullay infiltration. We present a case of granulocytic sarcoma of humerus which preceded the initial clinical manifestation of acute myeloid leukemia in a young patient which ultimately proved to be FABM2 variety. Though many tissues are affected by this tumour but the most favoured site is the bone. (+info)
Antigenicity of fusion proteins from sarcoma-associated chromosomal translocations.
(6/48)
Synovial sarcoma (SS), clear cell sarcoma (CCS), and desmoplastic small round cell tumor (DSRCT) are soft-tissue malignancies occurring primarily in adolescents and young adults. These tumors contain specific chromosomal translocations that fuse the 5' region of one gene with the 3' region of another, resulting in the formation of characteristic fusion proteins. These translocations are unique to tumor cells and may be required for persistence, thereby serving as targets for immunotherapy. It was hypothesized that the fusion breakpoint sequences associated with SS, CCS, and DSRCT can serve as tumor-specific neoantigens. To test this, peptides corresponding to the fusion breakpoints were designed and assessed for ability to bind to various class I HLA molecules. Two peptides derived from the SS breakpoint specifically bind the HLA-B7 antigen, and a 10-amino acid minimal epitope was identified for this interaction. Specific binding of a SS peptide and a CCS peptide to HLA-B27 molecule was also observed. Finally, a peptide designed from the DSRCT breakpoint specifically binds the HLA-A3 molecule, and a 9-amino acid optimal epitope was identified for this interaction. The physiological/immunological relevance of these peptide/MHC interactions was demonstrated by the induction of SS-specific CTLs from normal donor lymphocytes using in vitro stimulation with autologous, peptide-pulsed dendritic cells and by the ability of these CTLs to lyse human SS tumor cells endogenously expressing the full-length fusion protein. These results suggest that sequences in the fusion region of sarcoma-associated chimeras can bind class I HLA molecules and serve as neoantigens. These may be useful for the development of novel immunotherapies for sarcoma patients with appropriate HLA molecules and tumors bearing these translocations. (+info)
Gastrointestinal stromal tumors the assessment of malignant potential.
(7/48)
GISTS are the largest category of non-epithelial neoplasms of stomach and small bowel. Numerous immunohistochemical, ultrastructural and flow cytometry studies have been carried out for evaluation of prognostic factors which could predict malignant behaviour of these neoplasms. Tumor size of 5 cm and mitosis of 2/10 hpf were suggested as two important parameters which could predict the chances of recurrence and clinically aggressive course. The aim of this study is to examine predictive value of these two important parameters in assigning the tumors as high, intermediate and low risk groups. Using these two parameters we categorized 30 cases of GIST over a period of 6 years (1990-95) into low, intermediate and high risk groups and examined other features of these cases. Based on these two parameters alone we found that 4 cases each in low and intermediate group could be assigned to a higher risk group clinically as there were presence of adjacent organ infiltration, lymphatic emboli, serosal nodules, lymph node metastasis and transmural infiltration. Hence, other features like hemorrhage, necrosis and anaplasia should also be included in risk assessment. Metaplastic tissues like bone, cartilage and adipose tissues were seen only in high-risk categories. (+info)
PATHOLOGY OF TUMOURS IN CHILDREN.
(8/48)
An analysis of the types of tumour in children in the Manchester hospital region indicates that approximately two-thirds arose in the reticuloendothelial or nervous systems. The high mortality is largely due to the nature or site of the tumours, the majority of which cannot be eradicated by purely local measures. The most likely means of causing any significant improvement would be by greater centralization in the treatment of these children. (+info)