title: Have p53 gene mutations and protein expression a different biological significance in colorectal cancer?
abstract: p53 alterations are considered the most common genetic events in many types of neoplasms, including colorectal carcinoma (CRC). These alterations include mutations of the gene and/or overexpression of the protein. The aim of our study was to assess whether in 160 patients undergoing resective surgery for primary operable CRC there was an association between p53 mutations and protein overexpression and between these and other biological variables, such as cell DNA content (DNA-ploidy) and S-phase fraction (SPF), and the traditional clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and positive staining for p53 protein, detected with the monoclonal antibody DO-7, was present in 48% (77/160) of the cases, with agreement of 57% (91/160). In particular, a significant association was found between increased p53 expression and genetic alterations localized in the conserved regions of the gene or in the L3 DNA-binding domain and the specific type of mutation. Furthermore, both overexpression of p53 and mutations in the conserved areas of the gene were found more frequently in distal than in proximal CRCs, suggesting that they might be "biologically different diseases." Although p53 mutations in conserved areas were associated with flow cytometric variables, overexpression of p53 and mutations in its L3 domain were only related respectively to DNA-aneuploidy and high SPF. These data may reflect the complex involvement of p53 in the different pathways regulating cell-cycle progression. In conclusion, the combination of the mutational status and immunohistochemistry of p53, and flow cytometric data may provide an important insight into the biological features of CRCs.
authors.affiliation: Department of Oncology, Regional Reference Center for Biomolecular Characterization of Neoplasms and Genetics Screening of Hereditary Tumors of Sicily, University of Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.forename: Manuela
authors.initials: M
authors.lastname: Migliavacca
authors.forename: Carla
authors.initials: C
authors.lastname: Tubiolo
authors.forename: Marcella
authors.initials: M
authors.lastname: Macaluso
authors.forename: Ines
authors.initials: I
authors.lastname: Zanna
authors.forename: Simona
authors.initials: S
authors.lastname: Corsale
authors.forename: Antonella
authors.initials: A
authors.lastname: Amato
authors.forename: Valentina
authors.initials: V
authors.lastname: Calò
authors.forename: Gabriella
authors.initials: G
authors.lastname: Dardanoni
authors.forename: Vincenza
authors.initials: V
authors.lastname: Morello
authors.forename: Mario
authors.initials: M
authors.lastname: La Farina
authors.forename: Ida
authors.initials: I
authors.lastname: Albanese
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Tomasino
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D004247:DNA / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011446:Prospective Studies; D017434:Protein Structure, Tertiary / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D004247:DNA