Have p53 gene mutations and protein expression a different biological significance in colorectal cancer?
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.
Bazan
Viviana
V
Department of Oncology, Regional Reference Center for Biomolecular Characterization of Neoplasms and Genetics Screening of Hereditary Tumors of Sicily, University of Palermo, Italy.
Migliavacca
Manuela
M
Tubiolo
Carla
C
Macaluso
Marcella
M
Zanna
Ines
I
Corsale
Simona
S
Amato
Antonella
A
Calò
Valentina
V
Dardanoni
Gabriella
G
Morello
Vincenza
V
La Farina
Mario
M
Albanese
Ida
I
Tomasino
Rosa Maria
RM
Gebbia
Nicola
N
Russo
Antonio
A
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*
D016159:Tumor Suppressor Protein p53; D004247:DNA