Expression of Notch1 to -4 and their ligands in renal cell carcinoma: a tissue microarray study.

BACKGROUND: Mutations in signalling pathways essential for embryonic development often lead to tumourigenesis, as is also true for Notch. The aim of this study was to assess the relationship between Notch1 to -4 and their ligands with anatomopathological features of the patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: This study investigated the pattern of protein expression in RCC specimens using tissue microarray technology. A total of 80 paraffin-embedded RCC samples were retrospectively analysed together with ACHN and A.704 cell lines. RESULTS: Notch1 showed significant positive correlation with chromophobe RCC, no broken capsule, Furhman grade I and when the number of nodes involved was small [(N=1); p=0.039, 0.016, 0.037 and 0.001, respectively)]. Notch3 showed higher expression when the tumour was located in the right kidney (p=0.048). CONCLUSION: Notch1 may be useful in the future as a biomarker for the differential diagnosis of different RCC histological subtypes. Notch1 to -3 may also have potential use as a strong prognostic factor.

Relevant Networks involving the p53 Signalling Pathway in Renal Cell Carcinoma.

INTRODUCTION: Renal cell carcinoma is the most common type of kidney cancer. A better understanding of the critical pathways and interactions associated with alterations in renal function and renal tumour properties is required. Our final goal is to combine the knowledge provided by a regulatory network with experimental observations provided by the dataset. METHODS: In this study, a systems biology approach was used, integrating immunohistochemistry protein expression profiles and protein interaction information with the STRING and MeV bioinformatics tools. A group consisting of 80 patients with renal cell carcinoma was studied. The expression of selected markers was assessed using tissue microarray technology on immunohistochemically stained slides. The immunohistochemical data of the molecular factors studied were analysed using a parametric statistical test, Pearson's correlation coefficient test. RESULTS: Bioinformatics analysis of tumour samples resulted in 2 protein networks. The first network consists of proteins involved in the angiogenesis pathway and the apoptosis suppressor, BCL2, and includes both positive and negative correlations. The second network shows a negative interaction between the p53 tumour suppressor protein and the glucose transporter type 4. CONCLUSION: The comprehensive pathway network will help us to realise the cooperative behaviours among pathways. Regulation of metabolic pathways is an important role of p53. The pathway involving the tumour suppressor gene p53 could regulate tumour angiogenesis. Further investigation of the proteins that interact with this pathway in this type of tumour may provide new strategies for cancer therapies to specifically inhibit the molecules that play crucial roles in tumour progression.

Subacute cerebellar degeneration as paraneoplastic syndrome: initial symptom of breast cancer with HER2 overexpression.

We report the case of a patient with subacute cerebellar degeneration presenting as paraneoplastic syndrome, preceding the final diagnosis of breast cancer. The tumor had high HER2 overexpression, so a weekly regimen of paclitaxel/trastuzumab was started after surgery of the primary breast tumor. Negativity of specific antineuronal antibodies and clinical stabilization of the patient was achieved after 12 cycles of treatment. The interest of this case is the unusual presentation and the targeted therapeutic approach that has been used.