Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence

Abstract

To obtain a more integrated understanding of the different breast cancer phenotypes and to investigate whether biomolecular profiles can distinguish between specific histotypes, we explored the interrelations among several biologic variables indicative of, or related to, hormone dependence, proliferation and apoptosis control, and angiogenesis in ductal and lobular carcinomas, the most common histotypes. Oestrogen and progesterone receptors, tumour proliferative activity, the expression of cyclin A, p16 ink4A , p27 kip1 , p21 waf1 , p53, bcl-2, and levels of vascular endothelial growth factor and hypoxia-inducible factor1a (HIF-1a) were evaluated in 190 in ductal and 67 lobular carcinomas. Our findings support the hypothesis that in ductal and lobular carcinomas are two distinct, partially phenotypically unrelated entities, the latter being characterised by the presence of features indicative of differentiation such as oestrogen receptors, low proliferation and lack of p53 expression and associated with low vascular endothelial growth factor content compared to angiogenesis in ductal carcinomas. Conversely, no significant difference was found between lobular carcinomas and in ductal carcinomas considering the frequency distribution of PgRpositive cases, cyclin-dependent kinase inhibitors acting at the G1/S boundary, bcl-2 and HIF-1a protein expression. Although both generally defined as hormone responsive, in ductal and lobular carcinomas are also characterised by biologic patterns in which proteins related to hormone responsiveness, cell-cycle control, apoptosis and angiogenesis were differently associated. This finding suggests the need to refine breast cancer characterisation in order to provide detailed information about individual tumours, or subsets of tumours, that will help in defining optimal treatment approaches.

Molecular markers (c-erbB-2, p53) in breast cancer.

“…The percentage of c-erbB-2 positive cases increased along with tumor dimensions. These findings are consistent with literature data [5,[51][52][53][54][55]. We observed correlation, but not statistically important, between p53 expression and lymph node involvement.…”

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

“…However, IDC and ILC share certain characteristics in gene expression. Well differentiated IDC and ILC show similar expression of some proliferation and cell cycle regulated genes, including cyclin D1, p16, p27, mdm-2, and mib-1 (Geradts and Ingram, 2000;Soslow et al, 2000), and similar bcl-2 and HIF-1␣ expression (Coradini et al, 2002).…”

“…They differ in hormone receptor status with 55-72% of IDCs being estrogen receptor (ER) positive compared with 70 -92% of ILCs, and 33-70% of IDCs being progesterone receptor (PR) positive compared with 63-67% of ILCs (Harris et al, 2000). A number of proteins have also been found to be differentially expressed in IDC and ILC, including vimentin, cathepsin D, thrombospondin, E-cadherin, vascular endothelial growth factor, cytokeratin 8, and cyclin A (Domagala et al, 1990;Bedner et al, 1995;Serre et al, 1995;Berx et al, 1996;Lee et al, 1998;Lehr et al, 2000;Coradini et al, 2002). In addition, differences in genetic alterations in IDC and ILC have been observed.…”

Gene expression signatures in breast cancer distinguish phenotype characteristics, histologic subtypes, and tumor invasiveness

“…It has been established that invasive intraductal and lobular breast tumors have distinct histologies and clinical presentations. Lobular tumors often are ER-positive, tend to be more slowly proliferating, 25 and differ in DNA copy number changes from ductal cancers, suggesting a separate tumor progression pathway. 26,27 In the current study, cDNA microarrays were used to identify differential gene sequences in both tumor subtypes.…”