Wild type p73 overexpression and high-grade malignancy in breast cancer

The overexpression of wild type p73 is the most frequent alteration of p73 in malignancies. We investigated, in 70 breast carcinomas, p73 mRNA express ion and its relationship to p53 mutations, determined by an immunohistochem ical method, and loss heterozygosity (LOH) status of the 1p36 region, toget her with its possible implication in the pathogenesis of breast carcinomas. LOH, amplifying DNA by PCR using 5 markers, of 1p36 region (one intragenic to p73 gene) was found in 17% of cases but no significant correlation was observed with p73 overexpression. p53 positive immunostaining was present i n 33% of breast carcinomas, and these exhibited a statistically significant relation with p73 overexpressed tumors. Overexpression of p73 mRNA was obs erved in 19 tumors (27%). The analysis of cases with p73 overexpression and cases with normal mRNA expression, in terms of age and pathologic characte ristics of the tumors showed a significant association of p73 overexpressio n and tumors with lymph node metastases, vascular invasion and higher patho logic stage. These results suggest that p73 overexpression is a molecular a lteration that could be implicated in the tumorigenesis of breast carcinoma s and, eventually, in a poor clinical behavior.