RESUMEN
PURPOSE: Hepatocellular carcinoma (HCC) shows various molecular and genetic alterations in its development and progression. Recently, microsatellite instability (MSI) and the loss of heterozygosity (LOH), have been postulated as useful prognostic factors in many malignant tumors. LOH is related to the allelic loss of various tumor suppressor genes, however, MSI has been found to be the result of a mismatched DNA pairing. Our objectives were to evaluate MSI and p53 gene LOH and to correlate this to clinicopathological factors. METHODS: MSI analysis was performed by using polymerase chain reaction with 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346 and D17S250 recommended in the 1998 NCI International Workshop) on 50 surgically resected tumors. p53 LOH was detected with 4 markers (D17S796, TP53, D17S5, D17S513). RESULTS: MSI and p53 LOH were detected in 30% and 66%, respectively. 18% of HCCs exhibited MSI in 5 NCI-recommended markers and 18% of HCCs demonstrated MSI in 4 p53 markers. MSI was mostly detected in BAT25 and BAT26 markers. MSI was more frequently detected in tumor grade I, small HCC, and non-lymphovascular group. For the most part, p53 LOH was detected by D17S513 marker (38.1%). p53 LOH results were correlated with higher tumor grade and invasiveness. LOH-High group showed a significant correlation with advanced HCCs and lymphovascular invasion. There was no demonstrated correlation between MSI and p53 LOH was not demonstrated. CONCLUSION: These results suggest that MSI may be involved to some extent in hepatocarcinogenesis and tumor invasion. Also MSI and p53 gene LOH may be a useful clinical indicator in determining the prognosis among patients with HCC.
Asunto(s)
Humanos , Carcinoma Hepatocelular , ADN , Genes p53 , Genes Supresores de Tumor , Pérdida de Heterocigocidad , Inestabilidad de Microsatélites , Repeticiones de Microsatélite , Reacción en Cadena de la Polimerasa , Pronóstico , SuccinimidasRESUMEN
PURPOSE: Breast cancer shows various molecular and genetic alterations in its development and progression. Microsatellite alterations, and especially microsatellite instability (MSI) and loss of heterozygosity (LOH), have recently been postulated as a novel mechanism of carcinogenesis and as a useful prognostic factor for several gastrointestinal malignancies. LOH is related to the allelic loss of various tumor suppressor genes; however, MSI has been found to be the result of an erroneous DNA mismatch repair system and this has been known to be involved in the carcinogenesis of the hereditary non-polyposis colon cancers and some portion of the sporadic colorectal or gastric cancers. Yet MSI has rarely been studied in invasive ductal carcinoma. Our objectives were to evaluate the MSI and p53 protein expression in invasive ductal carcinomas and to correlate this with various clinicopathological factors. METHODS: The MSI analysis was performed by using polymerase chain reaction with five polymorphic microsatellite markers (the BAT25, BAT26, D2S123, D5S346 and D17S250 loci as recommended by the 1998 NCI International Workshop on Microsatellite Instabilitis and RER phenotypes) in 50 surgically resected tumors and each of their non-tumorous counterpart. The p53 protein expression was studied using immunohistochemistry. RESULTS: MSI and a p53 protein expression were detected in 22% and 54% of the tumors and non-tumorous tissues, respectively. MSI was more frequently detected in tumor grade I, T-stage I, non-metastatic tumor and tumor stage I. Also there were rare cases showing a high grade and stage with metastasis in the MSI-high group, in which more than 3 microsatellite loci had MSI. The p53 expression results correlated well with a higher tumor grade. Correlation between MSI and the p53 expression was not found. CONCLUSION: These results may suggest that MSI may be involved in some portions in mammary carcinogenesis and tumor invasion. Also the clinical use of the MSI status may help to determine a better prognosis among invasive ductal cancer patients.