Purpose: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ERa)^positive breast carcinoma but are not indicated for persons with ERa-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ERa-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERh, in patients treated with adjuvant tamoxifen. Experimental Design: We investigated ERh by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors. Results: ERh was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ERa-negative patients (P = 0.003; P = 0.04), but not in the ERa-positive subgroup (P = 0.49; P = 0.88). Lack of ERh conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ERanegative subgroup even after adjustment for other markers. ERa was an independent marker only within the ERh-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02).

Background: Soft tissue sarcoma (STS) diagnosis is challenging because of a multitude of histopathological subtypes, different genetic characteristics, and frequent intratumoral pleomorphism. One-third of STS metastasize and current risk-stratification is suboptimal, therefore, novel diagnostic and prognostic markers would be clinically valuable. We assessed the diagnostic and prognostic value of array-based gene expression profiles using 27 k cDNA microarrays in 177, mainly high-grade, STS of 13 histopathological subtypes.

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Global expression profiles of a consecutive series of 121 childhood acute leukemias (87 B lineage acute lymphoblastic leukemias, 11 T cell acute lymphoblastic leukemias, and 23 acute myeloid leukemias), six normal bone marrows, and 10 normal hematopoietic subpopulations of different lineages and maturations were ascertained by using 27K cDNA microarrays. Unsupervised analyses revealed segregation according to lineages and primary genetic changes, i.e., TCF3(E2A)͞PBX1, IGH@͞MYC, ETV6(TEL)͞RUNX1(AML1), 11q23͞MLL, and hyperdiploidy (>50 chromosomes). Supervised discriminatory analyses were used to identify differentially expressed genes correlating with lineage and primary genetic change. The gene-expression profiles of normal hematopoietic cells were also studied. By using principal component analyses (PCA), a differentiation axis was exposed, reflecting lineages and maturation stages of normal hematopoietic cells. By applying the three principal components obtained from PCA of the normal cells on the leukemic samples, similarities between malignant and normal cell lineages and maturations were investigated. Apart from showing that leukemias segregate according to lineage and genetic subtype, we provide an extensive study of the genes correlating with primary genetic changes. We also investigated the expression pattern of these genes in normal hematopoietic cells of different lineages and maturations, identifying genes preferentially expressed by the leukemic cells, suggesting an ectopic activation of a large number of genes, likely to reflect regulatory networks of pathogenetic importance that also may provide attractive targets for future directed therapies.