Purpose: To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC). Experimental Design: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Results: Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern (''metastatic signature'') derived from primary tumor was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described ''global'' metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Conclusion: Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.

A retrospective immunohistological analysis of 100 patients with pT1-3 N0 and pT1-3 N1 gastric adenocarcinoma demonstrated a high frequency of micro-involvement in the removed lymph nodes. The presence of three or more tumour cells in more than 10 per cent of the lymph nodes was of significant prognostic value in the pN0 cases. Multivariate analysis identified micro-involvement as an independent prognostic factor. The results explain why patients benefit from lymphadenectomy even if the removed lymph nodes are not involved by tumour (pN0) in routine histological examination. The frequent occurrence of micro-involvement is a strong argument favouring routine D2 lymph node dissection in gastric cancer surgery in patients with lymph node metastasis.

Non-invasive differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) is difficult. The aim of this study was to assess the accuracy of contrast-enhanced phase inversion ultrasound to differentiate between histologically proven FNH and HCA, analysing the arterial and (early) portal venous phase. 32 patients with histological proven FNH (n=24) or HCA (n=8) have been included in this prospective study. Examination technique: Siemens Elegra, phase inversion harmonic imaging (PIHI) with low mechanical index (MI)<0.2-0.3 using SonoVue (BR 1). The contrast enhancing tumour characteristics were evaluated during the hepatic arterial (starting 8-22 s) and early portal venous phase (starting 12-30 s). The image analysis was performed by three examiners. In 23 of 24 patients with FNH the contrast pattern revealed pronounced arterial and (early) portal venous enhancement. Homogeneous enhancement was detected during the hepatic arterial phase in all eight patients with HCA. In contrast to patients with FNH, no enhancement was seen during the portal venous phase. In conclusion, contrast-enhanced phase inversion ultrasound demonstrated pronounced arterial and portal venous enhancement in patients with focal nodular hyperplasia. In contrast, after homogeneous enhancement during hepatic arterial phase, no enhancement during hepatic portal venous phase was detected in patients with hepatocellular adenoma. Therefore, this technique might improve the functional characterization of benign hypervascular focal liver lesions.

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