1. 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
- Author
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BAZAN, Viviana, AGNESE, Valentina, CALO', Valentina, VALERIO, Maria Rosaria, LATTERI, Mario, VIENI, Salvatore, GRASSI, Nello, CICERO, Giuseppe, TOMASINO, Rosa Maria, GEBBIA, Nicolo', RUSSO, Antonio, CORSALE, S, DARDANONI, G, COLUCCI, G, BAZAN, V, AGNESE, V, CORSALE, S, CALO', V, VALERIO, MR, LATTERI, M, VIENI, S, GRASSI, N, CICERO, G, DARDANONI, G, TOMASINO, RM, COLUCCI, G, GEBBIA, N, RUSSO, A, and Vieni, S.
- Subjects
Male ,Oncology ,Multivariate analysis ,Colorectal cancer ,polymerase chain reaction ,medicine.medical_treatment ,Leucovorin ,Colorectal Neoplasm ,medicine.disease_cause ,Bioinformatics ,Exon ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,exon ,gene mutation ,multivariate analysi ,Prospective cohort study ,single strand conformation polymorphism MeSH: Adenocarcinoma ,protein p53 EMTREE medical terms: adult ,Proto-Oncogene Protein ,Mutation ,article ,protein domain ,clinical trial ,Hematology ,Middle Aged ,aged ,Italy ,priority journal ,Chemotherapy, Adjuvant ,Lymphatic Metastasis ,Disease Progression ,Female ,Fluorouracil ,Colorectal Neoplasms ,cancer tissue ,prognosi ,prospective study ,Human ,sampling ,medicine.medical_specialty ,folinic acid ,gene sequence ,Adenocarcinoma ,rectum carcinoma ,Proto-Oncogene Proteins p21(ras) ,outcomes research ,Proto-Oncogene Proteins ,Internal medicine ,medicine ,Humans ,controlled study ,neoplasms ,Gene ,Neoplasm Staging ,Chemotherapy ,EMTREE drug terms: fluorouracil ,levamisole ,Antineoplastic Combined Chemotherapy Protocol ,controlled clinical trial ,business.industry ,fluorouracil ,K ras protein ,protein p53 adult ,codon ,colon adenocarcinoma ,colorectal surgery ,human ,human cell ,human tissue ,major clinical study ,male ,multivariate analysis ,oncology ,prediction ,prognosis ,sequence analysis ,single strand conformation polymorphism Adenocarcinoma ,Aged ,Levamisole ,Multivariate Analysis ,ras Proteins ,Tumor Suppressor Protein p53 [EMTREE drug terms] ,Lymphatic Metastasi ,ras Protein ,medicine.disease ,Prospective Studie ,sequence analysi ,Tumor Suppressor Protein p53 ,business - Abstract
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.
- Published
- 2005
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