Correlation of numerical and structural status of chromosome 16 with histological type and grade of non-invasive and invasive breast carcinomas

Abstract

Loss of heterozygosity on chromosome arm 16q frequently occurs in human breast carcinomas regardless of the histological grade or type. To reveal whether the status of chromosome 16 corresponds to the histology of breast carcinomas, we examined the signal number of 16cen, 16q breakpoints and 1;16 fusions in the interphase nuclei of 185 breast carcinomas using fluorescence in situ hybridization to detect the loci D16Z2 (16cen), D16Z3 (16q11), D16S154 (16q24) and D1Z1 (1q12). A 16q loss associated with a proximal or distal breakage was identified as a discrepancy between the modal signal counts of the D16Z2, D16Z3 and D16S154 loci in each tumor. Clonal 16cen aneusomy, proximal breakages, distal breakages and 1;16 fusion were detected in 62%, 35%, 34% and 38% of the carcinomas respectively. Each of these alterations correlated with the histology of both non-invasive and invasive carcinomas; 16cen aneusomy was more frequent in carcinomas of high histologic grade, proximal breakage was more frequent in invasive ductal carcinomas (IDCs) of the strand or solid types and in grade-2 and -3 carcinomas, and distal breakage was more frequent in tubular/cribriform type IDCs and grade-1 carcinomas. 1;16 fusion correlated with the tubular/cribriform type of non-invasive or invasive carcinomas and invasive lobular carcinomas. Proximal breakage correlated with 16cen aneusomy, whereas the distal breakage correlated with 16cen disomy. These structural and numerical chromosome alterations appeared to occur in association with each other, and their specific combinations appeared to be involved in the establishment of morphological variety among breast carcinomas. Int. J. Cancer (Pred. Oncol.) 84:381-387, 1999.