TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer

Daniela Kandioler, Ronald Zwrtek, Carmen Ludwig, Elisabeth Janschek, Meinhard Ploner, Friedrich Hofbauer, Irene Kührer, Sonja Kappel, Friedrich Wrba, Manfred Horvath, J. Karner, Karl Renner, Michael Bergmann, Judith Karner-Hanusch, Richard Pötter, Raimund Jakesz, Bela Teleky, Friedrich Herbst

Research output: Article

67 Citations (Scopus)

Abstract

Objective: To evaluate and compare the predictive power of p53 gene analysis versus p53 immunohistochemical staining in terms of response to preoperative short-term radiotherapy using 25 Gy in operable rectal cancer. Summary Background Data: Recent studies show that p53 may be a determinant of radio-sensitivity being required for induction of apoptosis in case of radiation-induced DNA damage. Methods: Preirradiation biopsy samples of 64 patients with rectal carcinoma were analyzed. Genetic alterations of the p53 gene were detected by complete direct sequencing of exons 2 to 10. Expression of the nuclear phosphoprotein p53 was assessed by immunohistochemical staining. Results were correlated with histopathology of resected specimens and follow-up data, respectively. Results: Mutations of the p53 gene were present in 45% of tumors. Patients with a normal p53 gene had a significant survival advantage. Comparing pre- and postradiotherapy T category, a reduction was seen in patients with normal p53 genotype only. A mutant p53 genotype was highly specific in indicating stable disease concerning T category after irradiation. Protein overexpression was detected in 61%. Overexpression of the p53 protein was not related to survival or response. The concordance between immunohistochemistry and sequencing was only 0.51. Conclusions: The authors show that downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival.

Original languageEnglish
Pages (from-to)493-498
Number of pages6
JournalAnnals of Surgery
Volume235
Issue number4
DOIs
Publication statusPublished - 2002

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p53 Genes
Rectal Neoplasms
Radiotherapy
Genotype
Survival
Immunohistochemistry
Radiation
Staining and Labeling
Phosphoproteins
Radio
DNA Damage
Exons
Neoplasms
Proteins
Apoptosis
Carcinoma
Biopsy
Mutation

ASJC Scopus subject areas

  • Surgery

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TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer. / Kandioler, Daniela; Zwrtek, Ronald; Ludwig, Carmen; Janschek, Elisabeth; Ploner, Meinhard; Hofbauer, Friedrich; Kührer, Irene; Kappel, Sonja; Wrba, Friedrich; Horvath, Manfred; Karner, J.; Renner, Karl; Bergmann, Michael; Karner-Hanusch, Judith; Pötter, Richard; Jakesz, Raimund; Teleky, Bela; Herbst, Friedrich.

In: Annals of Surgery, Vol. 235, No. 4, 2002, p. 493-498.

Research output: Article

Kandioler, D, Zwrtek, R, Ludwig, C, Janschek, E, Ploner, M, Hofbauer, F, Kührer, I, Kappel, S, Wrba, F, Horvath, M, Karner, J, Renner, K, Bergmann, M, Karner-Hanusch, J, Pötter, R, Jakesz, R, Teleky, B & Herbst, F 2002, 'TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer', Annals of Surgery, vol. 235, no. 4, pp. 493-498. https://doi.org/10.1097/00000658-200204000-00006
Kandioler, Daniela ; Zwrtek, Ronald ; Ludwig, Carmen ; Janschek, Elisabeth ; Ploner, Meinhard ; Hofbauer, Friedrich ; Kührer, Irene ; Kappel, Sonja ; Wrba, Friedrich ; Horvath, Manfred ; Karner, J. ; Renner, Karl ; Bergmann, Michael ; Karner-Hanusch, Judith ; Pötter, Richard ; Jakesz, Raimund ; Teleky, Bela ; Herbst, Friedrich. / TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer. In: Annals of Surgery. 2002 ; Vol. 235, No. 4. pp. 493-498.
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abstract = "Objective: To evaluate and compare the predictive power of p53 gene analysis versus p53 immunohistochemical staining in terms of response to preoperative short-term radiotherapy using 25 Gy in operable rectal cancer. Summary Background Data: Recent studies show that p53 may be a determinant of radio-sensitivity being required for induction of apoptosis in case of radiation-induced DNA damage. Methods: Preirradiation biopsy samples of 64 patients with rectal carcinoma were analyzed. Genetic alterations of the p53 gene were detected by complete direct sequencing of exons 2 to 10. Expression of the nuclear phosphoprotein p53 was assessed by immunohistochemical staining. Results were correlated with histopathology of resected specimens and follow-up data, respectively. Results: Mutations of the p53 gene were present in 45{\%} of tumors. Patients with a normal p53 gene had a significant survival advantage. Comparing pre- and postradiotherapy T category, a reduction was seen in patients with normal p53 genotype only. A mutant p53 genotype was highly specific in indicating stable disease concerning T category after irradiation. Protein overexpression was detected in 61{\%}. Overexpression of the p53 protein was not related to survival or response. The concordance between immunohistochemistry and sequencing was only 0.51. Conclusions: The authors show that downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival.",
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T1 - TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer

AU - Kandioler, Daniela

AU - Zwrtek, Ronald

AU - Ludwig, Carmen

AU - Janschek, Elisabeth

AU - Ploner, Meinhard

AU - Hofbauer, Friedrich

AU - Kührer, Irene

AU - Kappel, Sonja

AU - Wrba, Friedrich

AU - Horvath, Manfred

AU - Karner, J.

AU - Renner, Karl

AU - Bergmann, Michael

AU - Karner-Hanusch, Judith

AU - Pötter, Richard

AU - Jakesz, Raimund

AU - Teleky, Bela

AU - Herbst, Friedrich

PY - 2002

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N2 - Objective: To evaluate and compare the predictive power of p53 gene analysis versus p53 immunohistochemical staining in terms of response to preoperative short-term radiotherapy using 25 Gy in operable rectal cancer. Summary Background Data: Recent studies show that p53 may be a determinant of radio-sensitivity being required for induction of apoptosis in case of radiation-induced DNA damage. Methods: Preirradiation biopsy samples of 64 patients with rectal carcinoma were analyzed. Genetic alterations of the p53 gene were detected by complete direct sequencing of exons 2 to 10. Expression of the nuclear phosphoprotein p53 was assessed by immunohistochemical staining. Results were correlated with histopathology of resected specimens and follow-up data, respectively. Results: Mutations of the p53 gene were present in 45% of tumors. Patients with a normal p53 gene had a significant survival advantage. Comparing pre- and postradiotherapy T category, a reduction was seen in patients with normal p53 genotype only. A mutant p53 genotype was highly specific in indicating stable disease concerning T category after irradiation. Protein overexpression was detected in 61%. Overexpression of the p53 protein was not related to survival or response. The concordance between immunohistochemistry and sequencing was only 0.51. Conclusions: The authors show that downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival.

AB - Objective: To evaluate and compare the predictive power of p53 gene analysis versus p53 immunohistochemical staining in terms of response to preoperative short-term radiotherapy using 25 Gy in operable rectal cancer. Summary Background Data: Recent studies show that p53 may be a determinant of radio-sensitivity being required for induction of apoptosis in case of radiation-induced DNA damage. Methods: Preirradiation biopsy samples of 64 patients with rectal carcinoma were analyzed. Genetic alterations of the p53 gene were detected by complete direct sequencing of exons 2 to 10. Expression of the nuclear phosphoprotein p53 was assessed by immunohistochemical staining. Results were correlated with histopathology of resected specimens and follow-up data, respectively. Results: Mutations of the p53 gene were present in 45% of tumors. Patients with a normal p53 gene had a significant survival advantage. Comparing pre- and postradiotherapy T category, a reduction was seen in patients with normal p53 genotype only. A mutant p53 genotype was highly specific in indicating stable disease concerning T category after irradiation. Protein overexpression was detected in 61%. Overexpression of the p53 protein was not related to survival or response. The concordance between immunohistochemistry and sequencing was only 0.51. Conclusions: The authors show that downstaging after short-term radiation may occur but is seen in tumors with normal p53 gene only. Moreover, p53 genotype but not p53 immunohistochemistry is predictive for response to preoperative short-term radiotherapy and patient survival.

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