Abstract
p53 protein detected immunohistochemically has not been accepted as a biomarker for breast cancer patients because of disparate reports of the relationship between the amount of p53 protein detected and patient survival. The purpose of this study was to determine experimental conditions and methods of data analysis for which p53 stain intensity could be prognostic for survival of young breast cancer patients. A tissue microarray of specimens from 93 patients was stained with anti-p53 antibody, and stain intensity measured with a computer-aided image analysis system. A cut-point at one standard deviation below the mean of the distribution of p53 stain intensity separated patients into two groups with significantly different survival. These results were confirmed by Quantitative Nuclear Grade determined by DNA-specific Feulgen staining. P53 provided information beyond ER and PR status. Therefore, under the conditions reported here, p53 protein can be an effective prognostic factor for young breast cancer patients.
Highlights
Mutations in the p53 gene are common in many tumors, including breast tumors (Osborne et al, 1991)
We found that p53 protein stain intensity measured by quantitative image analysis can distinguish patients with good and poor survival, and provide information beyond that provided by the patient’s estrogen receptor status and progesterone receptor status
Of the total of 171 patients with tissue on the microarray, 93 patients who had been treated with adjuvant hormone therapy, chemotherapy, or both, and who's pairs of disks had sufficient tissue were analyzed for p53 stain intensity
Summary
Mutations in the p53 gene are common in many tumors, including breast tumors (Osborne et al, 1991) Many of these mutations result in an accumulation of the mutant form of the p53 protein (Hainaut & Hollstein, 2000). In breast carcinoma patients having lumpectomy and radiation therapy, overexpression of mutant p53 protein was reported to be significantly prognostic for ipsilateral breast tumor recurrence (Turner et al, 2000). A non-linear relationship between stain intensity and patient survival has been reported; medium stain intensity was associated with better survival than high or low stain intensity (Camp et al, 2004). The latter two reports used image analysis to quantify p53 stain intensity, the others used visual judgment to score p53 staining
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