Different Gene Expression Patterns in Invasive Lobular and Ductal Carcinomas of the Breast

Abstract

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological types of breast cancer worldwide. Whereas IDC incidence has remained stable, ILC is the most rapidly increasing breast cancer phenotype in the United States and Western Europe. It is not clear whether IDC and ILC represent molecularly distinct entities and what genes might be involved in the development of these two phenotypes. We conducted comprehensive gene expression profiling studies to address these questions. Total RNA from 21 ILCs, 38 IDCs, two lymph node metastases, and three normal tissues were amplified and hybridized to ϳ42,000 clone cDNA microarrays. Data were analyzed using hierarchical clustering algorithms and statistical analyses that identify differentially expressed genes (significance analysis of microarrays) and minimal subsets of genes (prediction analysis for microarrays) that succinctly distinguish ILCs and IDCs. Eleven of 21 (52%) of the ILCs ("typical" ILCs) clustered together and displayed different gene expression profiles from IDCs, whereas the other ILCs ("ductal-like" ILCs) were distributed between different IDC subtypes. Many of the differentially expressed genes between ILCs and IDCs code for proteins involved in cell adhesion/motility, lipid/fatty acid transport and metabolism, immune/defense response, and electron transport. Many genes that distinguish typical and ductal-like ILCs are involved in regulation of cell growth and immune response. Our data strongly suggest that over half the ILCs differ from IDCs not only in histological and clinical features but also in global transcription programs. The remaining ILCs closely resemble IDCs in their transcription patterns. Further studies are needed to explore the differences between ILC molecular subtypes and to determine whether they require different therapeutic strategies.

Reproductive factors and subtypes of breast cancer defined by hormone receptor and histology

“…In general, the findings for ductolobular tumours were more similar to ductal than to lobular tumours. These findings are consistent with a recent gene expression study (Zhao et al, 2004), which found that about half of the lobular cancers had similar gene expression patterns to ductal tumours, while the remaining 'typical' lobular cancers had a different gene expression pattern. However, in these analyses we found little evidence that these reproductive factors act differently on either ductal or lobular tumours, with the possible exception that early age at first birth was most strongly associated with lower risk of lobular cancers, and that ductolobular tumours were associated with the strongest risk reduction per full-term pregnancy.…”

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms

“…A shorter latency period of ductal compared to lobular carcinoma obtained from our analysis could be due (at least in part) to higher proliferation and apoptosis [21]. Our results are also in agreement with other molecular studies on cancer proliferation, biology, and genetics, which demonstrated that lobular tumors exhibited similarities to low-grade ductal tumors [22][23][24]. Several studies have revealed a striking similarity between in situ and invasive breast cancers, where all markers correlated with grade rather than with tumor invasiveness [22,[25][26][27], and there was a good concordance between grade in primary and metastatic tumors [28][29][30].…”

The proteins FABP7 and OATP2 are associated with the basal phenotype and patient outcome in human breast cancer

“…Microarray-based class discovery studies pioneered by Perou and colleagues [1] have demonstrated that breast cancer could be classified into molecularly distinct groups based upon global gene expression profiles and their similarity to those of normal cell counterparts. Their results have subsequently been confirmed and expanded by multiple independent studies [2][3][4][5]. One of these biologically and clinically distinct groups, which has attracted attention in recent years as a molecularly distinct subtype of breast cancer with poor prognosis, is basal-like cancer [1,3,4,6].…”