Havep53 gene mutations and protein expression a different biological significance in colorectal cancer?

Viviana Bazan, Mario La Farina, Antonella Amato, Vincenza Morello, Ida Albanese, Nicolo' Gebbia, Valentina Calo', Antonio Russo, Nicola Gebbia, Antonio Russo, Gabriella Dardanoni, Ida Albanese, Rosa Maria Tomasino, Mario La Farina, Antonella Amato, Manuela Migliavacca, Simona Corsale

Risultato della ricerca: Article

18 Citazioni (Scopus)

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 over-expression 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.
Lingua originaleEnglish
pagine (da-a)237-246
Numero di pagine10
RivistaJournal of Cellular Physiology
Volume191
Stato di pubblicazionePublished - 2002

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Colorectal Neoplasms
Genes
Mutation
DNA
Proteins
S Phase
Surgery
Cells
Single-Stranded Conformational Polymorphism
Ploidies
Aneuploidy
Cell Cycle
Immunohistochemistry
Staining and Labeling
Polymerase Chain Reaction
Neoplasms

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cita questo

Havep53 gene mutations and protein expression a different biological significance in colorectal cancer? / Bazan, Viviana; La Farina, Mario; Amato, Antonella; Morello, Vincenza; Albanese, Ida; Gebbia, Nicolo'; Calo', Valentina; Russo, Antonio; Gebbia, Nicola; Russo, Antonio; Dardanoni, Gabriella; Albanese, Ida; Tomasino, Rosa Maria; Farina, Mario La; Amato, Antonella; Migliavacca, Manuela; Corsale, Simona.

In: Journal of Cellular Physiology, Vol. 191, 2002, pag. 237-246.

Risultato della ricerca: Article

Bazan, V, La Farina, M, Amato, A, Morello, V, Albanese, I, Gebbia, N, Calo', V, Russo, A, Gebbia, N, Russo, A, Dardanoni, G, Albanese, I, Tomasino, RM, Farina, ML, Amato, A, Migliavacca, M & Corsale, S 2002, 'Havep53 gene mutations and protein expression a different biological significance in colorectal cancer?', Journal of Cellular Physiology, vol. 191, pagg. 237-246.
Bazan, Viviana ; La Farina, Mario ; Amato, Antonella ; Morello, Vincenza ; Albanese, Ida ; Gebbia, Nicolo' ; Calo', Valentina ; Russo, Antonio ; Gebbia, Nicola ; Russo, Antonio ; Dardanoni, Gabriella ; Albanese, Ida ; Tomasino, Rosa Maria ; Farina, Mario La ; Amato, Antonella ; Migliavacca, Manuela ; Corsale, Simona. / Havep53 gene mutations and protein expression a different biological significance in colorectal cancer?. In: Journal of Cellular Physiology. 2002 ; Vol. 191. pagg. 237-246.
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title = "Havep53 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 over-expression 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.",
author = "Viviana Bazan and {La Farina}, Mario and Antonella Amato and Vincenza Morello and Ida Albanese and Nicolo' Gebbia and Valentina Calo' and Antonio Russo and Nicola Gebbia and Antonio Russo and Gabriella Dardanoni and Ida Albanese and Tomasino, {Rosa Maria} and Farina, {Mario La} and Antonella Amato and Manuela Migliavacca and Simona Corsale",
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T1 - Havep53 gene mutations and protein expression a different biological significance in colorectal cancer?

AU - Bazan, Viviana

AU - La Farina, Mario

AU - Amato, Antonella

AU - Morello, Vincenza

AU - Albanese, Ida

AU - Gebbia, Nicolo'

AU - Calo', Valentina

AU - Russo, Antonio

AU - Gebbia, Nicola

AU - Russo, Antonio

AU - Dardanoni, Gabriella

AU - Albanese, Ida

AU - Tomasino, Rosa Maria

AU - Farina, Mario La

AU - Amato, Antonella

AU - Migliavacca, Manuela

AU - Corsale, Simona

PY - 2002

Y1 - 2002

N2 - 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 over-expression 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.

AB - 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 over-expression 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.

UR - http://hdl.handle.net/10447/76343

M3 - Article

VL - 191

SP - 237

EP - 246

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

ER -