[Analyses of p53 mutations in breast cancers with a combined use of yeast functional assay and immunohistochemical staining].
p53 status was examined in a total of 52 primary breast cancers, using a combination of yeast-based assay for transcriptional activity of p53 (yeast functional assay, YA) and immunohistochemical staining (IHC) for p53 protein accumulation. Results by the two methods were compared, and their correlations to the clinicopathological characteristics were analyzed. Nineteen cases (37%) were shown to have p53 mutations by YA, while 11 (21%) were shown to be positive of p53 accumulation by IHC. The tumors were classified into 4 groups according to the results by the two methods: Group I (8/52), YA (+) & IHC (+): Group II (11/52), YA (+) & IHC (-): Group III (3/52), YA (-) & IHC (+) and Group IV (30/52), YA (-) & IHC (-). DNA sequence analysis of all the YA (+) cases showed missense mutations in 7 out of 8 cases of Group I and nonsense or frameshift mutations in 8 out of 11 cases of Group II. The presence of p53 mutations significantly correlated with the absence of estrogen receptor in the tumors (Group I + II versus Group III + IV), whereas the number of stained cells positive of p53 did not. Microvascular invasion was significantly more frequent in Group I (75%) than in Group II (27%) (P < 0.05). Survival of the patients assessed by Kaplan-Meier method was the best in Group III, followed by Group IV, II and I (P < 0.05) in that order. These results indicate that tumor p53 status determined by the yeast functional assay and immunohistochemistry can serve as an important prognosticator for patients with breast cancer.
First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
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Takahashi
D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53