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Retention of the p53 Codon 72 Arginine Allele Is Associated with a Reduction of Disease-Free and Overall Survival in Arginine/Proline Heterozygous Breast Cancer Patients

Department of Experimental Pathology [M. B., F. F., C. B., E. M., C. T., G. S., C. F.], Breast Cancer Unit, Department of Pathology [C. C., D. S.], and Breast Cancer Surgical Unit, 1^st Surgical Clinic [M. T.], University of Bologna, 40126 Bologna; Center for Applied Biomedical Research, St. Orsola University Hospital, 40126 Bologna [C. C.]; and Department of Gerontological Research, Italian National Research Center on Aging, 60189 Ancona [F. O., C. F.], Italy

Purpose: The arginine to proline substitution at codon 72 represents a common aminoacidic polymorphism of the p53 protein. Recent data suggest that p53 codon 72 may modulate the response to cancer therapy. The aim of this study was to test the hypothesis that the p53 codon 72 genotype, evaluated in the tumor tissue and in the disease-free lymph node, is related to differences in disease-free and overall survival among breast cancer-affected patients.

Experimental Design: We assessed the p53 codon 72 genotype in DNA from disease-free lymph nodes and neoplastic tissues obtained from 67 women affected by breast cancer who underwent surgical resection at the Bologna Breast Cancer Surgical Unit from 1993 to 1995.

Results: We found that the retention of the p53 codon 72 arginine allele in the tumor tissue of proline/arginine heterozygous breast cancer patients is associated with statistically significant reduced disease-free and overall survivals.

Conclusions: Our findings suggest that the genotyping for p53 codon 72 locus in both the tumor tissue and in the lymph node of breast cancer patients could contribute to identify a subset of arginine/proline heterozygous patients who have a reduced survival that is associated with the specific retention of the arginine allele in the tumor tissue.

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