This new 1318-nm Nd:YAG laser facilitates complete resection of multiple bilateral centrally located metastases and thus is lobe sparing. Resection of 20 or more metastases is reasonable because long-term survival was significantly better than that observed with incomplete resection.
Our understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. Herein, transcriptome-wide expression profiles of a unique cohort of 20 laser-resected pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma (RCC) were analyzed to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and the number of Mets per patient. Differentially expressed genes were identified by comparing early (DFI 9 months) and late (DFI 5 years) Mets, and Mets derived from patients with few ( 8) and multiple ( 16) Mets. Early and late Mets could be separated by the expression of genes involved in metastasis-associated processes, such as angiogenesis, cell migration and adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an elevated expression of genes associated with cell division and cell cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from an increased growth potential. Minimal sets of genes for the prediction of the DFI and the number of Mets per patient were identified. Microarray results were confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In summary, we showed that subgroups of Mets are distinguishable based on their expression profiles, which reflect the DFI and the number of Mets of a patient. To what extent the identified molecular factors contribute to the development of these characteristics of metastatic spread needs to be analyzed in further studies. ' UICC Key words: kidney cancer; lung metastases; oligonucleotide microarraysIn numerous tumour types, the development of metastases (Mets) causes the patients' death. The median survival of renal cell carcinoma (RCC) patients amounts to merely 6 to 12 months after Mets have been diagnosed. 1 RCC is the urological cancer with the highest percentage of tumour-related deaths 2 because metastasis occurs in about 60% of the patients. 3 The preferential localization of RCC Mets is the lung. 1 In contrast to the emerging development of molecular-based therapies for RCC in the last few years, 3 molecular prognostic markers are still missing. Despite the knowledge of several molecular factors involved in metastatic spread like angiogenesis, cell adhesion, invasion or migration, 4,5 little is known about specific characteristics of this complex process. These are, for example, primary-dependent site-specific metastasis, 6 varying dormancy periods of Mets originating from the same primary tumour entity causing disease-free intervals (DFI) ranging from several months to many years, or the differing number of Mets in patients with the same primary tumour. Knowing the molecular fundamentals of these phenomena would support the prognosis of patients' outcome and facilitate the decision for an appropriate therapy regime, particularly in RCC where the DFI and the number of Mets are important predictors of clinical...
Currently used clinicopathological parameters are insufficient for a reliable prediction of metastatic risk and disease-free survival (DFS) of patients with clear-cell renal cell carcinoma (ccRCC). To identify prognostic genes, the expression profiles of primary ccRCC obtained from patients with different DFS -eight synchronously, nine metachronously and seven not metastasized tumors -were determined by genome-wide expression analyses. Synchronously and metachronously metastasized primary ccRCC differed in the expression of 167 genes. Thirty-six of these genes were also differentially expressed in synchronously vs. metachronously developed pulmonary metastases analyzed in a previous study. Because of their DFS-associated deregulation that is concordant in metastases and primary ccRCC, these genes are potentially functionally involved in metastatic tumor growth and are also prognostically useful. A prognostic impact was confirmed for the genes CD31, EDNRB and TSPAN7 at the mRNA level (n 5 86), and for TSPAN7 at the protein level (n 5 106). Patients with a higher gene expression of EDNRB or TSPAN7, or with TSPAN7-positive vessels in both cores investigated on tissue microarrays had a significantly longer DFS and tumor-specific survival (TSS). Patients with a higher CD31 gene expression showed a significantly longer TSS. EDNRB was an independent prognostic marker for the DFS. CD31, EDNRB and TSPAN7 had an independent impact on the TSS. In summary, comparative analysis of primary tumors and metastases is appropriate to identify independent prognostic markers in ccRCC. Gene expression of CD31 and EDNRB, and endothelial TSPAN7 protein level are potentially useful to improve outcome prediction because of their independent prognostic impact.The development of macroscopic metastases is the major cause of tumor-associated deaths. 1,2 Clear-cell renal cell carcinoma (ccRCC), which is the most frequent type of kidney cancer, 3 causes initial or metachronous metastases in about 50% of the patients. 4 The median five-year survival rate of patients with metastatic ccRCC accounts for only 11-20%. 5 The disease-free survival (DFS) until manifest metastases develop differs extremely in these patients and results in a very diverse disease outcome. The DFS reflects the dormancy period that tumor cells can undergo after they have settled in a secondary organ. This latency can persist for many years. 2 It is supposed to be caused by suppressed tumor cell proliferation, inhibited angiogenesis or antitumor immune responses. 6 Currently used clinicopathological parameters are insufficient for a reliable outcome prediction for ccRCC patients. The molecular prognostic markers known to date are not suitable for a routine clinical use. 7 Therefore, new molecular markers are urgently needed to predict individual metastatic risk and DFS of ccRCC patients. Such markers represent the
BACKGROUND: Lung cancer still remains one of the most commonly occurring solid tumors and even in stage Ia, surgery fails in 30% of patients who develop distant metastases. It is hypothesized that these must have developed from occult circulating tumor cells present at the time of surgery, or before. The aim of the present study was to detect such cells in the peripheral blood and to monitor these cells following surgery. METHODS: 30 patients treated for lung cancer with surgery were monitored for circulating epithelial cells (CEC) by taking peripheral blood samples before, 2 weeks and 5 months after surgery and/or radiotherapy (RT) chemotherapy (CT) or combined RT/CT using magnetic bead enrichment and laser scanning cytometry (MAINTRAC(R)) for quantification of these cells. RESULTS: In 86% of the patients CEC were detected before surgery and in 100% at 2 weeks and 5 months after surgery. In the control group, which consisted of 100 normal donors without cancer, 97 % were negative for CEC. A significantly higher number of CEC was found preoperatively in patients with squamous cell carcinoma than in those with adenocarcinoma. In correlation to the extent of parenchymal manipulation 2 weeks after surgery, an increase in numbers of CEC was observed with limited resections (18/21) whereas pneumonectomy led to a decrease (5/8) of CEC, 2 weeks after surgery. The third analysis done 5 months after surgery identified 3 groups of patients. In the group of 5 patients who received neo- or adjuvant chemo/radiotherapy there was evidence that monitoring of CEC can evaluate the effects of therapy. Another group of 7 patients who underwent surgery only showed a decrease of CEC and no signs of relapse. A third group of 11 patients who had surgery only, showed an increase of CEC (4 with an initial decrease after surgery and 7 with continuous increase). In the group with a continuous increase during the following 24 months, 2 early relapses in patients with stage Ia adenocarcinoma were observed. The increase of CEC preceded clinical detection by six months. CONCLUSION: We consider, therefore, that patients with adenocarcinoma and a continuous increase of CEC after complete resection for lung cancer are at an increased risk of early relapse.
Disclosure: Gaetano Rocco, MD, has received travel reimbursements from Covidien. Federico Venuta, MD, has received travel reimbursements from Nicomed and Ethicon.
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