Biomarkers in carcinoma of the human breast

• Grant number: 95/00537-4
• Support Opportunities: Research Projects - Thematic Grants
• Start date: January 01, 1996
• End date: April 30, 1998
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ricardo Renzo Brentani
• Grantee: Ricardo Renzo Brentani
• Host Institution: Instituto Ludwig de Pesquisa sobre o Câncer (ILPC). São Paulo , SP, Brazil

Abstract

In the present study we have attempted to determine the incidence and nature of TP53 and p16 mutations as well as mRNA expression of plasminogen activators (tPA and uPA) and metalloproteinases (gelatinases A and B, stromelysin 3 (ST3) and matrilysin) in a breast tumor samples from a group of Brazilian patients. Using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis, we screened DNA samples from paired tumors and normal tissue from 206 patients with primary breast tumors and 45 patients with fibroadenoma for the occurrence of genetic alterations in TP53 and 90 primary breast carcinomas were examined for the occurrence of mutations in the exon 1 of the p16. None of the tumors analyzed showed mutations or homozygous deletions for p16. Loss of heterozygosis (LOH) at TP53 was also investigated in both series using a PCR-based polymorphic marker. Of 206 primary breast tumors analyzed 56 (27%) showed evidence for TP53 mutations. Mutations were observed among all exons examined (4 to 9), but with a prevalence for exon 7 (p=0.02). In the primary breast tumors examined loss of heterozygosis was observed in 37% (60/164) of the informative cases and there was a significant association between the occurrence of TP53 mutations and LOH (p=0.01). None of the fibroadenomas analyzed showed TP53 mutations or LOH. No statistically significant associations were observed with age, tumor size, histological type, lymph node involvement or steroid hormone receptors and TP53 genetic alterations. Higher incidence of TP53 mutations was detected in advanced tumors. High mRNA levels of uPA, ST3 and matrilysin were statistically more frequent in 81 carcinomas than in the adjacent breast tissues. Paired normal tissue samples generally produced weaker signals of gelatinases A and B when compared to the corresponding tumor. A correlation was found among the mRNA levels of ST3, uPA, tPA and gelatinase A and B, suggesting a regulated transcription. (AU)