In situ quantification of aberrant p53 in colorectal neoplasia.
Aberrant p53 protein accumulation was measured immunohistologically in 342 colorectal paraffin-embedded tissue sections from 115 patients (24 with adenocarcinoma, 59 with adenoma and 32 'hospital controls'). Subjective scoring was compared with quantitative cell imaging, including dichotomous (p53+/p53-) status, ng p53mut mg(-1) enterocyte protein, and tumour burden and patient body 'burden' of aberrant p53. A total of 62.5% cancer patients, 23.7% adenoma patients and 3.1% hospital controls were accorded p53+ status on the basis of p53 quantification. Quantitative p53+/p53- assignment had a stronger inverse association with survival (chi2=6.17, p=0.013, Kaplan-Meier test) than subjective 'visual estimation' (chi2=0.57, p=0.449). There was a strong inverse relationship between the p53 'body burden' and the months of post-diagnosis survival (hazard ratio=1.42, p=0.0004, Cox proportional hazards). Absolute quantification for inactivated p53 permits objective and reproducible scoring, adjusts for intra-laboratory immunostaining 'batch effects', corrects for fixation artefacts, and standardizes for inter-laboratory differences in fixation, antibody selection and staining method. Clinically, in situ quantification of p53 will permit more accurate survival prognoses and will inform therapy selection and dose. Ultimately, accurate quantitative tissue/blood p53 correlations may provide a minimally invasive and systemic surrogate measure for these same clinical purposes.
Smith
Steven Jay
SJ
VA-New York Harbor Health Care System, Brooklyn, New York 11209, USA. smithstevenjay@netscape.net
Neugut
Alfred
A
Heitjan
Daniel
D
Forde
Kenneth
K
Holt
Peter
P
Santella
Regina M
RM
Jiin-Chyuan
Luo
L
Carney
Walter
W
Ward
Llewelyn
L
Brandt-Rauf
Paul W
PW
D000230:Adenocarcinoma; D000236:Adenoma; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D011379:Prognosis; D012720:Severity of Illness Index; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
D000951:Antigens, Neoplasm; D016159:Tumor Suppressor Protein p53