Analysis of gene expression in ductal carcinoma in situ of the breast.

PURPOSE The risk of recurrence and progression of ductal carcinoma in situ (DCIS) of the breast is best designated by morphological indicators, including the presence of necrosis. Our purpose was to identify molecular alterations underlying progression of DCIS. EXPERIMENTAL DESIGN We have compared gene expression within a cohort of six cases of DCIS with necrosis (DCIS(necrosis+)) and four cases without necrosis (DCIS(necrosis-)) using microdissection and cDNA microarray. RESULTS A set of 69 cDNAs from a group of 1,181 was identified that were consistently differentially expressed. Among this set, the mRNA for angio-associated migratory cell protein and a serine threonine protein kinase, nuclear Dbf2 related, were consistently higher in DCIS(necrosis+) and were also found to be overexpressed in the T47D breast cancer cell line subjected to hypoxia. Further study of angio-associated migratory cell protein by quantitative reverse transcriptase-PCR and in situ hybridization analysis of 37 cases of DCIS confirmed higher mRNA expression in DCIS(necrosis+) (P = 0.0095). CONCLUSIONS This study shows that although levels of gene expression are mostly similar between morphologically different DCIS, consistent differences in expression of a subset of genes can be identified between DCIS with and without necrosis.