LOSS OF HETEROZYGOSITY AT THE TP53 GENE - INDEPENDENT OCCURRENCE FROMGENETIC INSTABILITY EVENTS IN NODE-NEGATIVE BREAST-CANCER

TP53 abnormalities have been reported as an early event in the process of cellular transformation of human breast cancers, and involved in m ammary-tumor evolution, from in situ to invasive disease. to this stud y, node negative (N-) tumors were examined for TP53 allelic loss in re lation to different genetic instability events, including allelic loss at chromosome 17p13.3 and c-H-ras-1 loci, as well as alteration of th e c-myc and c-erbB-2/neu oncogenes. TP53 allelic loss was analyzed to determine whether such an abnormality was the more important, among ot her genetic events, in the N- tumors, whether it appeared independentl y 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 appe ars 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 parame ters, significant associations were observed only with estrogen-recept or-negative tumors (p = 0.05). Our results demonstrate that LOH at TP5 3 arises more frequently in the N- breast cancer, thus supporting earl ier findings suggesting that TP53 abnormality has a role early in the pathogenesis of breast lesions. Moreover, the data indicate that accum ulation of many genetic events occurs at a low level in N- breast tumo rs, and that TP53 abnormality occurs independently of these genetic ev ents. (C) 1997 Wiley-Liss, Inc.