Osteosarcoma is a genetically complex malignancy, predominantly afflicting the adolescent population and associated still with relatively poor long-term outcomes. Although there has been some improvement in the understanding of osteosarcoma biology, this has not yet translated particularly well into therapeutic advances. By using a whole-genome tiling path array for comparative genomic hybridization analysis, we sought to evaluate DNA copy number changes in 22 osteosarcoma tumor samples. Regions of most frequent gains or losses generated by Genomic Identification of Significant Targets in Cancer analysis were evaluated for genes of interest. Correlation of the copy number data with preexisting expression data for these genes yielded not only targets known to be important in osteosarcoma but also novel targets, notably cyclin E1. Fluorescence in situ hybridization and immunohistochemical analysis confirmed the findings. Overexpression of cyclin E1 has potential prognostic and therapeutic implications that are discussed herein.
Endometriosis does occur in postmenopausal women but is less common, is present in smaller volumes, and is less active. It has the same immunohistochemical profile as the disease occurring in premenopausal women and we infer from this that it has the potential to reactivate given the appropriate stimulation.
e19516 Background: Anthracycline based chemotherapy is the treatment of choice for aggressive primary lymphomas of the GI tract, with surgery reserved for management of complications. We report long term follow up of 71 cases of primary GI NHL treated with chemotherapy and/or surgery. Methods: Cases were identified from the institutional histology database & records reviewed. Results: 71 patients over an 24 year period were identified; 43 (61%) male, 28 (39%) female. Median age at diagnosis was 60 (15–83). 52 (73%) were DLBCL, 11 (16%) were T-cell, 8 (11%) were MALT. The 8 patients with MALT were treated with single agent chemotherapy; 7 (88%) are alive at median follow up of 8.5 years (2–16). Of the aggressive lymphomas (63), all patients with T cell lymphoma had small bowel as primary site and histological evidence of celiac associated enteropathy, even in the absence of known celiac disease. Primary sites of DLBCL were stomach 35 (67%), small bowel 11 (21%) & colon 6 (12%). 39 (62%) patients underwent surgery at diagnosis due to acute presentation with perforation, bleeding or obstruction, or to obtain histology. Following confirmed diagnosis, 61 patients received anthracycline based chemotherapy. 2 patients with T cell lymphoma presented with perforation, were treated with surgery only and died of rapid disease progression. Of the 63 patients with aggressive NHL, 37 (59%) remain alive & disease free at median follow up of 13 years (1–24). 35 (67%) patients with DLBCL are alive & disease free. Only 2 (18%) of the T cell lymphomas are alive & disease free. 5 deaths in the DLBCL group were not related to cancer or treatment. All deaths in the T cell group were due to progressive disease. There was no difference in survival between patients treated with chemotherapy only and those who also underwent surgery. Conclusions: Patients with aggressive primary B cell GI NHL have almost 70 % survival following anthracycline based chemotherapy. However, in contrast, coeliac enteropathy associated T-cell lymphomas present with rapidly progressive disease & have a survival of < 20% with chemotherapy and/or surgery. A novel therapeutic approach is required to improve outcome in this group. No significant financial relationships to disclose.
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