Loss of heterozygosity at theTP53 gene: Independent occurrence from genetic instability events in node-negative breast cancer

Abstract

TP53 abnormalities have been reported as an early event in the process of cellular transformation of human breast cancers, and involved in mammary-tumor evolution, from in situ to invasive disease. In this study, node-negative (N 2 ) tumors were examined for TP53 allelic loss in relation to different genetic instability events, including allelic loss at chromosome 17p13.3 and c-H-ras-1 loci, as well as alteration of the c-myc and c-erbB-2/neu oncogenes. TP53 allelic loss was analyzed to determine whether such an abnormality was the more important, among other genetic events, in the N 2 tumors, whether it appeared independently of these genetic events, and whether accumulation of genetic events arises in this group of breast tumors. Clinicopathological parameters were also examined. Loss of heterozygosity (LOH) at the TP53 gene appears the most frequent alteration detected (26% vs. 13%, 8%, 9% and 3% for LOH at D17S30 and c-H-ras-1 loci, and amplification of c-myc and c-erbB-2/neu respectively). There was no association between LOH at the TP53 locus and other genetic events. Among clinicopathological parameters, significant associations were observed only with estrogen-receptor-negative tumors (p 5 0.05). Our results demonstrate that LOH at TP53 arises more frequently in the N 2 breast cancer, thus supporting earlier findings suggesting that TP53 abnormality has a role early in the pathogenesis of breast lesions. Moreover, the data indicate that accumulation of many genetic events occurs at a low level in N 2 breast tumors, and that TP53 abnormality occurs independently of these genetic events. Int.

Genetic alterations in early-onset invasive breast carcinomas: Correlation of c-erbB-2 amplification detected by fluorescenceIn situ hybridization with p53 accumulation and tumor phenotype

“…In the present study, using the same probe as Xing et al (1996) we observed high levels of amplification at a lower frequency. The 9% incidence of c‐ erb B‐2 amplification that we observed in the control series featuring older patients with node‐negative breast cancers is similar to the 9 to 10% rate reported in 2 large series of patients from Australia and France (Seshadri et al, 1996; Lizard‐Nacol et al, 1997). The relatively high frequency of c‐ erb B‐2 amplification (38 to 68%) in breast cancer in young women reported by Xing et al (1996) is equal to or greater than the 18 to 39% range of c‐ erb B‐2‐gene amplification or p185erbB2‐protein over‐expression reported for non‐EOBC (review by Ross and Fletcher, 1998; Press et al, 1997).…”

Genetic alterations in early‐onset invasive breast carcinomas: Correlation of c‐erbB‐2 amplification detected by fluorescence In situ hybridization with p53 accumulation and tumor phenotype

“…In the present study, using the same probe as Xing et al (1996) we observed high levels of amplification at a lower frequency. The 9% incidence of c-erbB-2 amplification that we observed in the control series featuring older patients with node-negative breast cancers is similar to the 9 to 10% rate reported in 2 large series of patients from Australia and France (Seshadri et al, 1996;Lizard-Nacol et al, 1997). The relatively high frequency of c-erbB-2 amplification (38 to 68%) in breast cancer in young women reported by Xing et al (1996) is equal to or greater than the 18 to 39% range of c-erbB-2-gene amplification or p185erbB2protein over-expression reported for non-EOBC (review by Ross and Fletcher, 1998;Press et al, 1997).…”

Correlation between p53, c-erbB-2, and topoisomerase II? expression, DNA ploidy, hormonal receptor status and proliferation in 356 node-negative breast carcinomas: prognostic implications

“…Mutations and deletions of the p53 gene are relatively common in mammary carcinomas 2 and appear to occur early in carcinogenesis. 3 Most of them result in abrogation of the growth inhibitory or apoptotic potential of the encoded protein and thus facilitate unrestrained proliferation and progressive genomic instability (reviewed in refs 4 and 5). HER-2/neu, the gene coding for c-erbB-2, a tyrosine kinase receptor sharing sequence homologies with the epidermal growth factor receptor (EGFR), 6 is frequently amplified in ductal carcinomas of the breast, 7,8 which appears to be associated with a more aggressive behaviour of the tumours.…”