Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence.
To obtain a more integrated understanding of the different breast cancer phenotypes and to investigate whether bio-molecular 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 factor-1alpha (HIF-1alpha) 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 PgR-positive cases, cyclin-dependent kinase inhibitors acting at the G1/S boundary, bcl-2 and HIF-1alpha 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.
Coradini
D
D
Department of Experimental Oncology, Determinants of Prognosis and Treatment Response Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy. coradini@istitutotumori.mi.it
Pellizzaro
C
C
Veneroni
S
S
Ventura
L
L
Daidone
M G
MG
D017209:Apoptosis; D015415:Biomarkers; D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D014157:Transcription Factors / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D016228:Endothelial Growth Factors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors