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In situ quantification of aberrant p53 in colorectal neoplasia

机译：大肠肿瘤中p53异常的原位定量

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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 p53~(mut) 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 (χ~2 = 6.17, p = 0.013, Kaplan-Meier test) than subjective 'visual estimation' (χ~2 = 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.
机译：在115例患者（24例腺癌，59例腺瘤和32例“医院对照”）的342个结直肠石蜡包埋的组织切片中，通过免疫组织学方法检测了异常的p53蛋白积累。将主观评分与定量细胞成像进行比较，包括二分（p53〜+ / p53〜-）状态，ng p53〜（mut）mg〜（-1）肠上皮细胞蛋白，肿瘤负荷和患者身体异常p53的负担。根据p53定量，共有62.5％的癌症患者，23.7％的腺瘤患者和3.1％的医院对照组被赋予p53〜+状态。定量的p53〜+ / p53〜-分配与生存成反比关系（χ〜2 = 6.17，p = 0.013，Kaplan-Meier检验）比主观“视觉估计”（χ〜2 = 0.57，p = 0.449）强。 p53的“身体负担”与诊断后的生存期之间存在很强的反比关系（危险比= 1.42，p = 0.0004，Cox比例危险）。灭活的p53的绝对定量可实现客观且可重复的评分，调整实验室内免疫染色的“批效应”，校正固定假象，并标准化实验室间固定，抗体选择和染色方法的差异。临床上，对p53进行原位定量将可以更准确地预测生存情况，并为治疗选择和剂量提供依据。最终，准确的定量组织/血液p53相关性可以为这些相同的临床目的提供微创和全身替代指标。

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