Undifferentiated and poorly differentiated thyroid tumors are responsible for more than half of thyroid cancer patient deaths in spite of their low incidence. Conventional treatments do not obtain substantial benefits, and the lack of alternative approaches limits patient survival. Additionally, the absence of prognostic markers for well-differentiated tumors complicates patient-specific treatments and favors the progression of recurrent forms. In order to recognize the molecular basis involved in tumor dedifferentiation and identify potential markers for thyroid cancer prognosis prediction, we analysed the expression profile of 44 thyroid primary tumors with different degrees of dedifferentiation and aggressiveness using cDNA microarrays. Transcriptome comparison of dedifferentiated and well-differentiated thyroid tumors identified 1031 genes with >2-fold difference in absolute values and false discovery rate of o0.15. According to known molecular interaction and reaction networks, the products of these genes were mainly clustered in the MAPkinase signaling pathway, the TGF-b signaling pathway, focal adhesion and cell motility, activation of actin polymerization and cell cycle. An exhaustive search in several databases allowed us to identify various members of the matrix metalloproteinase, melanoma antigen A and collagen gene families within the upregulated gene set. We also identified a prognosis classifier comprising just 30 transcripts with an overall accuracy of 95%. These findings may clarify the molecular mechanisms involved in thyroid tumor dedifferentiation and provide a potential prognosis predictor as well as targets for new therapies.
Objective. Audit of women with invasive cervical cancer (CC) is critical for quality control within screening activities. We analysed the screening history in the 10 years preceding the study entry in women with and without CC during 2000–2011. Methods. 323 women with CC from six pathology departments in Catalonia (Spain) and 23,782 women with negative cytology were compared. Age, previous history of cytologies, and histological type and FIGO stage were collected from the pathology registries. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI95%). Results. History of cytology was registered in 26.2% of CC cases and in 78% of the control women (P < 0.0001) and its frequency decreased with increasing age. Compared to women with squamous cell carcinoma, adenocarcinoma cases were significantly more likely to have a cytology within the 3-year interval preceding cancer diagnosis (OR = 2.6 CI 95%: 1.2–5.6) and to have normal cytology results in previous screenings (OR = 2.4 CI 95%: 1.2–4.5). FIGO II–IV cases were more common among older women (older than 60 years). Conclusions. Absence of prior screening history was extremely common among CC cases compared to controls. Organized actions to reduce underscreened women and use of highly sensitive HPV-based tests could be important to reduce CC burden.
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