BACKGROUNDThe term poorly differentiated (PD) carcinoma was proposed 20 years ago to define aggressive, follicular‐derived thyroid carcinomas with behavior intermediate between follicular/papillary and anaplastic carcinomas. Among the variable histologic patterns recognized in such tumors, trabecular‐insular‐solid (TIS) areas usually are predominant. Conversely, some authors pointed out that PD carcinomas are characterized by unequivocal, high‐grade histology with atypias, high mitotic counts, and necrosis rather than by a specific growth pattern.METHODSThe clinicopathologic features of a series of 183 thyroid carcinomas with predominant (n = 165 tumors) or focal (n = 18 tumors) TIS growth patterns were studied by univariate and multivariate overall survival analyses and were compared with clinical outcomes. Subgroups included tumors with predominant oxyphilic features (n = 66 tumors) and (residual) papillary carcinoma features (n = 24 tumors). Control groups of papillary (n = 68 tumors), follicular (n = 71 tumors), and anaplastic (n = 35 tumors) carcinomas also were included for overall survival analysis.RESULTSTIS carcinomas had an intermediate behavior between papillary/follicular and anaplastic carcinomas (P < 0.0001). Univariate and multivariate statistical analyses demonstrated that age > 45 years (P = 0.007), the presence of necrosis (P < 0.0001), and a mitotic count > 3 per 10 high‐power fields (P = 0.01) were associated with poor outcome. A simplified scoring system based on statistically significant parameters allowed the identification of three prognostic subgroups (P < 0.0001).CONCLUSIONSPD TIS carcinomas overall followed a more aggressive course compared with differentiated thyroid carcinomas, irrespective of the extent of the TIS component. However, a numeric scoring system applied to specific clinicopathologic parameters further may identify three prognostic categories of patients who have significantly different survival rates at 5 years and 10 years. Cancer 2004;100:950–7. © 2004 American Cancer Society.

BackgroundOsteosarcoma (OS) is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable and no significant improvement has been observed in the last 20 years. Therefore, the search for alternative agents in OS is mandatory.ResultsWe investigated phospho-ERK 1/2, MCL-1, and phospho-Ezrin/Radixin/Moesin (P-ERM) as potential therapeutic targets in OS. Activation of these pathways was shown by immunohistochemistry in about 70% of cases and in all OS cell lines analyzed. Mutational analysis revealed no activating mutations in KRAS whereas BRAF gene was found to be mutated in 4/30 OS samples from patients. Based on these results we tested the multi-kinase inhibitor sorafenib (BAY 43-9006) in preclinical models of OS. Sorafenib inhibited OS cell line proliferation, induced apoptosis and downregulated P-ERK1/2, MCL-1, and P-ERM in a dose-dependent manner. The dephosphorylation of ERM was not due to ERK inhibition. The downregulation of MCL-1 led to an increase in apoptosis in OS cell lines. In chick embryo chorioallantoic membranes, OS supernatants induced angiogenesis, which was blocked by sorafenib and it was also shown that sorafenib reduced VEGF and MMP2 production. In addition, sorafenib treatment dramatically reduced tumour volume of OS xenografts and lung metastasis in SCID mice.ConclusionIn conclusion, ERK1/2, MCL-1 and ERM pathways are shown to be active in OS. Sorafenib is able to inhibit their signal transduction, both in vitro and in vivo, displaying anti-tumoural activity, anti-angiogenic effects, and reducing metastatic colony formation in lungs. These data support the testing of sorafenib as a potential therapeutic option in metastatic or relapsed OS patients unresponsive to standard treatments.

Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy.

SummaryBackground Fine-needle aspiration biopsy (FNAB) is the primary means to distinguish benign from malignant nodules and select patients for surgery. However, adjunctive diagnostic tests are needed because in 20-40% of cases the FNAB result is uncertain. Objective We investigated whether a search for the oncogenes RET/PTC, TRK and BRAF V600E in thyroid aspirates could refine an

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