The p53 Mutation and DNA Ploidy in Human Metastatic Breast Cancer

Cho, Seong Jin; Kim, Ae Ree; Won, Nam Hee

Abstract

The p53 gene, one of the tumor suppressor genes, is believed to play an important role through mutation and overexpression in the progression of various human malignant tumors. To compare the p53 mutation status between the primary and metastatic lesions of breast cancers and to investigate the mutational pattern of p53, immunohistochemistry (IHC) and polymerase chain reaction and single strand conformational polymorphism (PCR-SSCP) were performed in 25 cases of breast cancers with paraffin embedded tissue. Mutant protein products or point mutation were detected through IHC or PCR-SSCP method. And flow cytometrical (FCM) analysis were performed in the same paraffin blocks to correlate the DNA ploidy and p53 mutation. The following results are summarized. 1. The detection of the p53 gene mutation and overexpression of the p53 protein were measured in 40% and 48%, respectively, in 25 primary tumors, either or both methods was detected in 64%. 2. A concordance rate of the p53 protein expression between the primary and metastatic lesions of 25 breast cancers was 100%, but the concordance rate of the p53 gene mutation was 72%. 3. The correlation between the p53 mutation and the DNA aneuploidy was not statistically significant (p=0.38) 4. A p53 mutation by IHC or PCR-SSCP was more frequently detected in grade III breast cancers than in grade I or II. 5. Among 5 to 9 exons of the p53 gene, exon 7 was the most frequent mutation spot in this study. 6. Additional mutation of the p53 gene was developed in the three metastatic lesions. With the above results it is suggested that the p53 protein overexpression by immunohistochemistry is not correlated with the p53 mutation by PCR-SSCP. The p53 mutation pattern between the primary and metastatic lesions are not idenitical and an additional point mutation can occur in the metastatic lesion. The DNA aneuploidy is more frequently detected in the cases with the p53 protein overexpression than in the p53 protein negative, but it is not statistically significant.