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Nm23-H1 expression does not predict clinical survival in colorectal cancer patients
Authors:Dusonchet Luisa  Corsale Simona  Migliavacca Manuela  Calò Valentina  Bazan Viviana  Amato Antonella  Cammareri Patrizia  Totaro Maria Serena  Agnese Valentina  Cascio Sandra  La Rocca Gaspare  Sisto Pasqua Sandra  Dardanoni Gabriella  Valerio Maria Rosaria  Grassi Nello  Latteri Stefania  Cajozzo Massimo  Buscemi Maria  Castorina Sergio  Morello Vincenza  Tomasino Rosa Maria  Gebbia Nicola  Russo Antonio
Affiliation:Department of Pharmacology, University of Palermo, Palermo, Italy.
Abstract:
The gene Nm23, which encodes for a nucleoside diphosphate kinase, has been defined as a metastasis-suppressor gene because of the inverse correlation between its expression and the metastatic capacity of the tumor cells. For colorectal cancer, however, the findings are equivocal. The aim of our study was to assess, in 160 patients undergoing surgery for colorectal cancer (CRC), the expression of the Nm23-H1 protein and to evaluate its possible associations with traditional clinicopathologic variables, with DNA-ploidy and proliferative activity (S-phase fraction, SPF), and with disease-free and overall survival of patients. Nm23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry; DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. The median follow-up time in our study group was 71 months (range 34-115 months). No association was observed between Nm23-H1 protein expression and clinicopathological variables, S-phase fraction and DNA-ploidy. Furthermore, no significant differences were observed in the survival of patients with either moderate or strong Nm23-H1 expression. The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA aneuploid tumors and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death. Our results indicate that Nm23-H1 activity is tissue-specific and that in CRCs the expression of the protein is not associated with tumor progression and patient prognosis, although further studies are required in order to throw more light on the possible clinical significance of the overexpression of the protein Nm23-H1 in such tumors.
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