Detection of p53 gene mutations in fine-needle aspiration biopsied breast cancer specimens: correlations with nuclear p53 accumulations and tumor DNA aneuploidy patterns.
Using the polymerase chain reaction and a single strand conformation polymorphism (PCR-SSCP) analysis, p53 gene mutations have been examined preoperatively in aspirated biopsy specimens from 22 breast cancers. In eight (36%) of the studied cases, abnormal bands indicating mutations were detected and were more frequently present in common invasive breast carcinomas. Eight of the breast cancer cases were found to be positive for mutations: direct DNA sequencing confirmed eight mutations and revealed G to A and A to G nucleotide changes in five (63%) and two (25%) cases, respectively. The mutations that were localized at the CpG site of the gene were seen in three cases. Additionally, an immunohistochemical investigation of the presence of the p53 protein and a DNA flow-cytometrical analysis of the 22 resected breast cancers were also performed. Nuclear p53 protein accumulations and a DNA aneuploidy pattern were detected in 11 (50%) cases and in 16 (73%) cases, respectively, and both significantly correlated with p53 gene mutations (P < 0.01 and P < 0.001, respectively; Fisher's exact test). In contrast, in five cases of a breast cancer with a lower histologic grade, no p53 gene mutations, nuclear p53 protein accumulations, or DNA aneuploidy patterns were detected. These results thus suggest that p53 gene mutations, nuclear accumulations of the p53 protein, and a DNA aneuploidy pattern are events that occur with close relationship in the progression of a breast cancer, and that p53 abnormalities appear to correlate with a high grade of the malignancy. Therefore, the detection of p53 gene mutations in aspirated biopsy specimens of breast cancers may be helpful for an accurate and rapid cytological diagnosis, which reflects the prognosis.
Sato
T
T
First Department of Surgery, Sapporo Medical University, School of Medicine, Chuo-ku, Japan.
Yuyama
Y
Y
Watabe
K
K
Okazaki
A
A
Toda
K
K
Okazaki
M
M
Hirata
K
K
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000235:genetics*; D002467:Cell Nucleus / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D016159:Tumor Suppressor Protein p53