Anaplastic thyroid tumors exhibit considerable derangement of their cell cycle and multiple signal transduction pathways that leads to uncontrolled cellular proliferation and the development of genomic instability. This report is the first to comprehensively evaluate a panel of molecular targets for therapy of anaplastic thyroid cancer and supports the development of clinical trials with agents such as cetuximab, small-molecule tyrosine kinase inhibitors, and aurora kinase inhibitors, which may offer new hope for individuals diagnosed with this fatal thyroid malignancy.

BackgroundMDT (multidisciplinary team) meetings are considered an essential component of care for patients with cancer. However there is remarkably little direct evidence that such meetings improve outcomes. We assessed whether or not MDT (multidisciplinary team) processes influenced survival in a cohort of patients with colorectal cancer.MethodsObservational study of a population-based cohort of 586 consecutive patients with colorectal cancer diagnosed in Tayside (Scotland) during 2006 and 2007.ResultsRecommendations from MDT meetings were implemented in 411/586 (70.1 %) of patients, the MDT+ group. The remaining175/586 (29.9 %) were either never discussed at an MDT, or recommendations were not implemented, MDT- group. The 5-year cause-specific survival (CSS) rates were 63.1 % (MDT+) and 48.2 % (MDT-), p < 0.0001. In analysis confined to patients who survived >6 weeks after diagnosis, the rates were 63.2 % (MDT+) and 57.7 % (MDT-), p = 0.064. The adjusted hazard rate (HR) for death from colorectal cancer was 0.73 (0.53 to 1.00, p = 0.047) in the MDT+ group compared to the MDT- group, in patients surviving >6 weeks the adjusted HR was 1.00 (0.70 to 1.42, p = 0.987). Any benefit from the MDT process was largely confined to patients with advanced disease: adjusted HR (early) 1.32 (0.69 to 2.49, p = 0.401); adjusted HR(advanced) 0.65 (0.45 to 0.96, p = 0.031).ConclusionsAdequate MDT processes are associated with improved survival for patients with colorectal cancer. However, some of this effect may be more apparent than real – simply reflecting selection bias. The MDT process predominantly benefits the 40 % of patients who present with advanced disease and conveys little demonstrable advantage to patients with early tumours. These results call into question the current belief that all new patients with colorectal cancer should be discussed at an MDT meeting.

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5556 Background: Anaplastic thyroid cancer arises as a consequence of tumor progression, or transformation, from pre-existing differentiated thyroid cancer. Mutation of the p53 tumor-suppressor gene represents a common event in thyroid tumor progression. MDM2 encodes a protein that complexes with p53, downregulates its function, and leads to its degradation via a ubiquitin-proteasome pathway. The objective of this study was to evaluate the change in p53 and MDM2 expression in the transformation of differentiated to anaplastic thyroid carcinoma. Methods: Of 94 cases of anaplastic thyroid cancer diagnosed and treated in British Columbia Canada over a 20 year period (1984–2004) 32 cases (34%) had adequate tissue available for evaluation and 12 of these cases had associated foci of differentiated thyroid carcinoma. A tissue microarray was constructed from these 12 anaplastic thyroid tumors and their associated differentiated foci. Immunohistochemistry was utilized to evaluate expression of p53 and MDM2 by these tumors. Results: There was decreased expression of p53 and MDM2 by the anaplastic tumors when compared to the differentiated thyroid tumors from which they evolved. The expression of p53 and MDM2 was 17% and 8%, respectively, by the differentiated thyroid carcinoma, and 83% and 25%, respectively, by the anaplastic tumors. Evaluating the anaplastic cancers and the differentiated foci from which they evolved, p53 overexpression developed in 8 (67%) of tumors and MDM2 overexpression developed in 3 (25%) of tumors. All the anaplastic tumors that developed MDM2 overexpression also concurrently developed p53 overexpression. Conclusions: This report is the first to demonstrate derangement of p53, and its regulator, MDM2, is involved in the transformation of a subset of differentiated into anaplastic thyroid tumors. Isolated MDM2 overexpression does not appear to play an important role in anaplastic transformation of thyroid cancer. No significant financial relationships to disclose.