6533b85cfe1ef96bd12bc97d
RESEARCH PRODUCT
Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study
Viviana BazanValentina AgneseValentina Calo'Maria Rosaria ValerioMario LatteriSalvatore VieniNello GrassiGiuseppe CiceroRosa Maria TomasinoNicolo' GebbiaAntonio RussoSalvatore VieniS CorsaleG DardanoniG Coluccisubject
MaleOncologyMultivariate analysisColorectal cancerpolymerase chain reactionmedicine.medical_treatmentLeucovorinColorectal Neoplasmmedicine.disease_causeBioinformaticsExonAntineoplastic Combined Chemotherapy ProtocolsProspective Studiesexongene mutationmultivariate analysiProspective cohort studysingle strand conformation polymorphism MeSH: Adenocarcinomaprotein p53 EMTREE medical terms: adultProto-Oncogene ProteinMutationarticleprotein domainclinical trialHematologyMiddle AgedagedItalypriority journalOncologyChemotherapy AdjuvantLymphatic MetastasisDisease ProgressionFemaleFluorouracilColorectal Neoplasmscancer tissueprognosiprospective studyHumansamplingmedicine.medical_specialtyfolinic acidgene sequenceAdenocarcinomarectum carcinomaProto-Oncogene Proteins p21(ras)outcomes researchProto-Oncogene ProteinsInternal medicinemedicineHumanscontrolled studyneoplasmsGeneNeoplasm StagingChemotherapyEMTREE drug terms: fluorouracillevamisoleAntineoplastic Combined Chemotherapy Protocolcontrolled clinical trialbusiness.industryfluorouracil; folinic acid; K ras protein; levamisole; protein p53 adult; aged; article; cancer tissue; clinical trial; codon; colon adenocarcinoma; colorectal surgery; controlled clinical trial; controlled study; exon; gene mutation; gene sequence; human; human cell; human tissue; Italy; major clinical study; male; multivariate analysis; oncology; outcomes research; polymerase chain reaction; prediction; priority journal; prognosis; prospective study; protein domain; rectum carcinoma; sampling; sequence analysis; single strand conformation polymorphism Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy Adjuvant; Colorectal Neoplasms; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Levamisole; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Mutation; Neoplasm Staging; Prospective Studies; Proto-Oncogene Proteins; ras Proteins; Tumor Suppressor Protein p53 [EMTREE drug terms]human cellLymphatic Metastasipredictionras Proteinmedicine.diseasemajor clinical studyhuman tissueProto-Oncogene Proteins p21(ras)K ras proteinProspective Studiecolon adenocarcinomaMultivariate AnalysisMutationras Proteinscolorectal surgerysequence analysicodonTumor Suppressor Protein p53businessdescription
BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showed mutations in 43% (68/160) of the cases, while mutation analyses of exon 2 of the Ki-ras gene showed mutations in 46% (74/160) of the cases. Multivariate analyses showed that clinical outcome were strongly associated with the presence of specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13. CONCLUSION: Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic CRC.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-01-01 | Annals of Oncology |