TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer.
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.
Kandioler
Daniela
D
Department of Surgery, University of Vienna, Vienna, Austria. daniela.kandioler@akh-wien.ac.at
Zwrtek
Ronald
R
Ludwig
Carmen
C
Janschek
Elisabeth
E
Ploner
Meinhard
M
Hofbauer
Friedrich
F
Kührer
Irene
I
Kappel
Sonja
S
Wrba
Friedrich
F
Horvath
Manfred
M
Karner
Josef
J
Renner
Karl
K
Bergmann
Michael
M
Karner-Hanusch
Judith
J
Pötter
Richard
R
Jakesz
Raimund
R
Teleky
Bela
B
Herbst
Friedrich
F
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