Monosomy of chromosome 8 could be considered as a primary preneoplastic event in breast cancer: A preliminary study

Abstract

This pilot study analyzed and compared the presence of chromosome 8 aneusomy in Mexican women with breast cancer and adjacent, intraductal, proliferative lesions. To determine the chromosome 8 copy number, we performed fluorescence in situ hybridization in nine patients (1800 cells) who underwent mastectomy. We selected two tissue samples from each patient, one corresponding to the invasive ductal carcinoma (IDC) and the other adjacent to the intraductal proliferative lesion (IPL). Breast tissue from 17 autopsy samples (1700 cells) was used as a control. The number of cells with monosomy, disomy and polysomy per subject and type of tissue were compared among the three groups of tissue with the RxC statistical software package using 50,000 total replicates. Chromosome 8 aneusomy was found in 66 and 67% of cells from the IDC and IPL samples, respectively. Monosomy was detected significantly more frequently in IPL compared with IDC samples (49.11 vs. 27.11%; p=0.0000), whereas polysomy was significantly more frequent in IDC compared with IPL samples (40.11 vs. 16.99%; p=0.00000). Control cells showed 92.3% disomy. These findings suggest that polysomy of chromosome 8 is more frequently observed in IDC and that monosomy is more frequent in tissue of IPL. Therefore, monosomy may be considered as a primary preneoplastic event. Future studies should be performed to increase the amount of breast tissue with ductal proliferative changes and with cancer, in order to support the results of this pilot study.

Figure 1

(A) Preneoplastic lesion (usual intraductal hyperplasia). (H&E; LM, ×10). (B) Hyperplasia with DAPI (4′,6-diamidino-2-phenylindole), (FM, ×40). (C) Fluorescence in situ hybridization, probe CEP8 SpectrumOrange, Vysis (FM, ×63); bottom left, magnification of one signal (monosomy). (D) Ductal carcinoma (H&E; ML, ×10; ×40 bottom right). (E) Neoplastic cells with DAPI (MF, ×63). (F) Fluorescence in situ hybridization, probe CEP8 SpectrumOrange, Vysis (FM, ×63), bottom left, magnification of five signal (polysomy).