Clinicopathological variables used at present for prognostication and treatment selection for papillary thyroid carcinomas (PTCs) do not uniformly predict tumor behavior, necessitating identification of novel prognostic markers. Complicating the assessment is the long natural history of PTC and our rudimentary knowledge of its genetic composition. In this study we took advantage of differences in clinical behavior of two distinct variants of PTC, the aggressive tall-cell variant (TCV) and indolent conventional PTC (cPTC), to identify molecular prognosticators of outcome using complementary genome wide analyses. Comparative genome hybridization (CGH) and cDNA microarray (17,840 genes) analyses were used to detect changes in DNA copy number and gene expression in pathological cPTC and TCV. The findings from CGH and cDNA microarray analyses were correlated and validated by real-time PCR and immunohistochemical analyses on a series of 100 cases of cPTC and TCV. Genes identified by this approach were evaluated as prognostic markers in cPTC by immunohistochemistry on tissue arrays. CGH identified significant differences in the presence (76 versus 27%; P ‫؍‬ 0.001) and type of DNA copy number aberrations in TCV compared with cPTC. Recurrent gains of 1p34 -36, 1q21, 6p21-22, 9q34, 11q13, 17q25, 19, and 22 and losses of 2q21-31, 4, 5p14-q21, 6q11-22, 8q11-22, 9q11-32, and 13q21-31 were unique to TCV. Hierarchical clustering of gene expression profiles revealed significant overlap between TCV and cPTC, but further analysis identified 82 dysregulated genes differentially expressed among the PTC variants. Of these, MUC1 was of particular interest because amplification of 1q by CGH correlated with MUC1 amplification by real-time PCR analysis and protein overexpression by immunohistochemistry in TCV (P ‫؍‬ 0.005). Multivariate analysis revealed a significant association between MUC1 overexpression and treatment outcome, independent of histopathological categorization (P ‫؍‬ 0.03). Analysis of a validation series containing a matched group of aggressive and indolent cPTCs confirmed the association between MUC1 overexpression and survival (relative risk, 2.3; 95% confidence interval, 1.1-5.5; P ‫؍‬ 0.03). Our data suggest that MUC1 dysregulation is associated with aggressive behavior of PTC and may serve as a prognostic marker and potential therapeutic target in this disease.

No abstract

No abstract

Genomic instability as measured by inter-(simple sequence repeat) PCR was significantly higher for malignant diseases compared with benign thyroid tissues, but no such association was seen with aneuploidy or microsatellite instability.

INTRODUCTIONPyoderma gangrenosum (PG) is a rare, ulcerative inflammatory skin pathology frequently associated with systemic inflammatory disease. While rare after surgery, recognition of this disease in the post-surgical setting is important as it can mimic wound infection. There have been ten case reports to date of PG occurring immediately after cardiac surgery, with all of them presenting within the first week post-operatively.PRESENTATION OF CASEWe herein present a delayed and dramatic presentation of PG nine days after mitral valve replacement and repair of patent foramen ovale, two days after being discharged with a seemingly normal healing wound. Diagnosis of this disease in the postoperative period requires high suspicion when the characteristic ulcerative lesions are seen diffusely in all surgical wounds and show minimal improvement with antibiotic treatment or debridement.DISCUSSION/CONCLUSIONOur case highlights the importance of recognizing this disease in the postoperative period, even in a delayed presentation and initially limited to one of the surgical sites. This case calls for an awareness of this disease entity amongst cardiac surgeons as well as intensivists.