Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset

Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets

O papel da biópsia intraoperatória de congelação para os nódulos tireoidianos The role of intraoperative frozen sections for thyroid nodules

O valor da biópsia de congelação (BC) durante a tireoidectomia é controverso. OBJETIVO: Avaliar o papel da BC na conduta frente os nódulos tireoidianos. CASUÍSTICA E MÉTODO: Trabalho prospectivo de pacientes submetidos à cirurgia tireoidiana por doença nodular e com PAAF guiada por USG prévia em 2006. A BC intra-operatória foi classificada em benigna, maligna ou neoplasia folicular. PAAF, BC e exame de "parafina" foram comparados. RESULTADOS: À BC, 54% dos nódulos eram benignos, 30% neoplasia foliculares e 16% malignos. Todos os casos considerados benignos e malignos pela BC foram confirmados pelo exame de "parafina". Classificando as neoplásicas foliculares como "benignas" à BC, pois não possuem critério para indicação de tireoidectomia total, sensibilidade, especificidade, valores preditivos para os testes positivo e negativo e acurácia global foram, respectivamente, 69%, 100%, 100%, 91,5% e 77%. Casos classificados como "benignos" e "malignos" à PAAF foram confirmados pela BC e "parafina." Dentre os 42 casos de "neoplasia folicular" à PAAF, em um caso, a BC concluiu como carcinoma papilífero, em três, como benigno (confirmados pela "parafina"); e, em 38, manteve "padrão folicular", sendo 29 adenomas foliculares e nove carcinomas à "parafina". CONCLUSÕES: A BC somente está indicada nos casos cuja PAAF seja "neoplasia folicular."<br>The role of intraoperative frozen sections (FS) during thyroidectomy is controversial. AIM: to evaluate the role of FS for thyroid nodules management. PATIENTS AND METHODS: All patients who had thyroid surgery for nodular disease and previous USG-guided FNAB in 2006 were prospectively analyzed. They underwent intraoperative FS evaluation, and the biopsy material was classified as benign, malignant or follicular neoplasm. FNAB, FS and paraffin sections were compared. RESULTS: Under the FS, 54% of the nodules were benign, 30% were follicular neoplasms, and 16% were malignant. All cases considered benign and malignant under the FS evaluation were confirmed through the histological "paraffin" analysis. Since it is not considered a definitive indication for total thyroidectomy, if the follicular neoplasms were classified as "benign" under the FS, their sensitivity, specificity, positive and negative predictive values and global diagnostic accuracy were 69%, 100%, 100%, 91,5% e 77%, respectively. Among the 42 cases classified as "follicular neoplasm" under the FNAB, in 1 case the FS conclusion was for papillary carcinoma, in 3 cases as benign (all confirmed through the "paraffin"); and 38 cases continued as "follicular pattern", being 29 follicular adenomas and 9 carcinomas through the "paraffin". CONCLUSION: The FS is only indicated when the FNAB reports "follicular neoplasm"