p53 gene alterations in prostate cancer after radiation failure and their association with clinical outcome

A molecular and immunohistochemical analysis

Christiane Rakozy, David Grignon, YiWei Li, Edward Gheiler, Beena Gururajanna, J. Edson Pontes, Wael Sakr, David P. Wood, Fazlul H. Sarkar

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

This study evaluates the prevalence of p53 gene mutations in prostate cancer in salvage prostatectomies after radiation failure using single strand conformational polymorphism (SSCP) and direct sequencing of the polymerase chain reaction (PCR) product. Findings were correlated with immunohistochemically (IHC) detectable p53 expression in residual prostate cancer. The usefulness of p53 as a marker of clinical outcome was evaluated. Thirty-three cases were available for molecular and immunohistochemical analysis. Immunohistochemical stains for p53 were performed with clone DO7. PCR-SSCP for mutations in the coding region of p53 DNA (exons 4-9) was performed on all immunopositive cases and 12 of 23 immunonegative cases. All samples with an SSCP shift were sequenced for the respective exon. Patients were evaluated for biochemical failure for 1-82 months (median 38 months) following surgery. Immunohistochemical p53 reactivity was noted in 10 of 33 (30%) patients. Among p53 immunopositive cases SSCP shifts were seen in 7 of 10 (70%) samples with 5 of the 7 (71%) showing p53 mutations. Univariate analysis revealed abnormal expression of p53 protein by immunohistochemistry to be a significant predictor of poorer outcome (p = 0.025, log rank), however this was not independent of pathologic stage, surgical margin status and Gleason score. The presence of p53 gene mutations by PCR-SSCP and direct sequencing did not predict for outcome. In our study 30% of prostate cancers at the time of salvage prostatectomy after radiation failure expressed immunohistochemically detectable p53. PCR-SSCP and sequencing shows that not all of these cases have detectable mutations in the most frequent mutation sites (exons 4-9). Clinical failure is more common in the group of prostate cancer patients with abnormal p53 immunoreactivity.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalPathology Research and Practice
Volume195
Issue number3
StatePublished - 1999
Externally publishedYes

Fingerprint

p53 Genes
Prostatic Neoplasms
Radiation
Mutation
Exons
Polymerase Chain Reaction
Prostatectomy
Neoplasm Grading
Residual Neoplasm
Coloring Agents
Clone Cells
Cross-Sectional Studies
Biomarkers
Immunohistochemistry
DNA
Proteins

Keywords

  • Gene mutations
  • Immunohistochemistry
  • p53
  • Prostate cancer
  • Radiation therapy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

p53 gene alterations in prostate cancer after radiation failure and their association with clinical outcome : A molecular and immunohistochemical analysis. / Rakozy, Christiane; Grignon, David; Li, YiWei; Gheiler, Edward; Gururajanna, Beena; Pontes, J. Edson; Sakr, Wael; Wood, David P.; Sarkar, Fazlul H.

In: Pathology Research and Practice, Vol. 195, No. 3, 1999, p. 129-135.

Research output: Contribution to journalArticle

Rakozy, Christiane ; Grignon, David ; Li, YiWei ; Gheiler, Edward ; Gururajanna, Beena ; Pontes, J. Edson ; Sakr, Wael ; Wood, David P. ; Sarkar, Fazlul H. / p53 gene alterations in prostate cancer after radiation failure and their association with clinical outcome : A molecular and immunohistochemical analysis. In: Pathology Research and Practice. 1999 ; Vol. 195, No. 3. pp. 129-135.
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AB - This study evaluates the prevalence of p53 gene mutations in prostate cancer in salvage prostatectomies after radiation failure using single strand conformational polymorphism (SSCP) and direct sequencing of the polymerase chain reaction (PCR) product. Findings were correlated with immunohistochemically (IHC) detectable p53 expression in residual prostate cancer. The usefulness of p53 as a marker of clinical outcome was evaluated. Thirty-three cases were available for molecular and immunohistochemical analysis. Immunohistochemical stains for p53 were performed with clone DO7. PCR-SSCP for mutations in the coding region of p53 DNA (exons 4-9) was performed on all immunopositive cases and 12 of 23 immunonegative cases. All samples with an SSCP shift were sequenced for the respective exon. Patients were evaluated for biochemical failure for 1-82 months (median 38 months) following surgery. Immunohistochemical p53 reactivity was noted in 10 of 33 (30%) patients. Among p53 immunopositive cases SSCP shifts were seen in 7 of 10 (70%) samples with 5 of the 7 (71%) showing p53 mutations. Univariate analysis revealed abnormal expression of p53 protein by immunohistochemistry to be a significant predictor of poorer outcome (p = 0.025, log rank), however this was not independent of pathologic stage, surgical margin status and Gleason score. The presence of p53 gene mutations by PCR-SSCP and direct sequencing did not predict for outcome. In our study 30% of prostate cancers at the time of salvage prostatectomy after radiation failure expressed immunohistochemically detectable p53. PCR-SSCP and sequencing shows that not all of these cases have detectable mutations in the most frequent mutation sites (exons 4-9). Clinical failure is more common in the group of prostate cancer patients with abnormal p53 immunoreactivity.

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