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“Intrinsic Gene Expression” subtypes correlated with grade and morphometric parameters reveal a high proportion of aggressive basal-like tumors among black women of African ancestry
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2004
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Breast OncologyCancer PathologyGeneticsGenetic EpidemiologyPathologyDna Microarray StudiesGene Expression ProfilingTumor BiologyTumor HeterogeneityBlack WomenCancer Cell BiologyPublic HealthMolecular DiagnosticsAggressive Basal-like TumorsMolecular OncologyCancer ResearchMedicineBrca1 PathwayCancer GeneticsGene ExpressionMalignant DiseaseCancer RiskCancer EpidemiologyAfrican AncestryCancer GenomicsBreast CancerOncology
9509 Background: DNA microarray studies have identified 3 distinct subtypes of breast cancers (BC) based on “Intrinsic Gene Expression” patterns: basal-like tumors (ER-, HER2-), tumors with amplification of HER2/neu (ER-/+, HER2+), and luminal tumors (ER+, HER2-) (Perou et al. Nature 2000). BRCA1-associated BCs are characterized by poor differentiation, hormone receptor negativity, and a distinct basal-like pattern of gene expression. These aggressive features also characterize BC in women of African ancestry. In this study, we examined the proportion of BC within a given “intrinsic gene expression” subtype from a random cohort of Nigerians (N). Methods: H&E stained slides from archival BC, were evaluated for volume corrected mitotic index (smi), mean nuclear area (mna), and fraction of fields with tubular differentiation (ftd). Immunohistochemical staining for ER and HER2 were performed using Anti-ER (clone 6F11; 1:40, Novocastra) and rabbit antihuman HER2 antibody (1: 200; DAKO). Results: Of the 148 cases, 66.9% were premenopausal with a mean age of 43.8±11.2 years; large tumor size (mean 4.2±1.3cm); 77.8% had histological grade 2 or 3. ER expression was present in only 22.3% and HER2 was overexpressed in 18.9%. The proportion of tumors in each subtype was: ER-HER2- 87/148 (58.8%), HER2+ 28/148 (18.9%) and ER+ 33/148 (22.3%). Subtypes showed relatively weak association with clinical stage. However, overall grade and morphomety showed significant differences that persisted after adjustment for other patient and tumor characteristics (age, tumor size, and stage).Conclusions: The majority of BCs from Nigeria are basal-like, which suggest a distinct pathogenesis probably involving genes in the BRCA1 pathway. Future work will evaluate components of this pathway to develop more effective targeted therapies. No significant financial relationships to disclose.