title: TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer.
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.
  
  
  BACKGROUND
  Recent studies show that p53 may be a determinant of radiosensitivity 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.
authors.affiliation: Department of Surgery, University of Vienna, Vienna, Austria. daniela.kandioler@akh-wien.ac.at
authors.forename: Daniela
authors.initials: D
authors.lastname: Kandioler
authors.forename: Ronald
authors.initials: R
authors.lastname: Zwrtek
authors.forename: Carmen
authors.initials: C
authors.lastname: Ludwig
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Janschek
authors.forename: Meinhard
authors.initials: M
authors.lastname: Ploner
authors.forename: Friedrich
authors.initials: F
authors.lastname: Hofbauer
authors.forename: Irene
authors.initials: I
authors.lastname: Kührer
authors.forename: Sonja
authors.initials: S
authors.lastname: Kappel
authors.forename: Friedrich
authors.initials: F
authors.lastname: Wrba
authors.forename: Manfred
authors.initials: M
authors.lastname: Horvath
authors.forename: Josef
authors.initials: J
authors.lastname: Karner
authors.forename: Karl
authors.initials: K
authors.lastname: Renner
authors.forename: Michael
authors.initials: M
authors.lastname: Bergmann
authors.forename: Judith
authors.initials: J
authors.lastname: Karner-Hanusch
authors.forename: Richard
authors.initials: R
authors.lastname: Pötter
authors.forename: Raimund
authors.initials: R
authors.lastname: Jakesz
authors.forename: Bela
authors.initials: B
authors.lastname: Teleky
authors.forename: Friedrich
authors.initials: F
authors.lastname: Herbst
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D016158:Genes, p53 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics / Q000276:immunology; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011859:Radiography; D012004:Rectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome