Sonographic correlations with the new molecular classification of invasive breast cancer.

Ultrasound is a useful adjunct to mammography for the characterisation and biopsy of solid breast lesions. Protein expression profiling of breast cancer has identified specific subgroups with potential clinical, biological and therapeutic implications. The aim of this study was to determine the ultrasound correlates of these novel molecular classes of invasive breast cancer.

Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome.

Post-translational histone modifications are known to be altered in cancer cells, and loss of selected histone acetylation and methylation marks has recently been shown to predict patient outcome in human carcinoma. Immunohistochemistry was used to detect a series of histone lysine acetylation (H3K9ac, H3K18ac, H4K12ac, and H4K16ac), lysine methylation (H3K4me2 and H4K20me3), and arginine methylation (H4R3me2) marks in a well-characterized series of human breast carcinomas (n = 880). Tissue staining intensities were assessed using blinded semiquantitative scoring.

Forkhead-box A1 (FOXA1) expression in breast cancer and its prognostic significance.

The forkhead-box A1 (FOXA1) controls downstream transcription of oestrogen receptor (ER)-regulated genes. In this study, the biological and prognostic value of FOXA1 expression was assessed immunohistochemically in a large and well-characterised series of invasive breast carcinoma with a long term follow-up using tissue microarray. FOXA1 expression was associated with steroid hormone receptors (ERalpha, PgR and AR), other variables of good prognosis such as smaller tumour size, lower histological grade, luminal cytokeratins (CK18 and CK7/8), BRCA1 and E-cadherin.

Is acinic cell carcinoma a variant of secretory carcinoma? A FISH study using ETV6'split apart' probes.

Aims: Acinic cell carcinomas (ACCs) and secretory carcinomas (SCs) of the breast are rare, low-grade malignancies that preferentially affect young female patients. Owing to the morphological and immunohistochemical similarities between these lesions, they have been proposed to be two morphological variants of the same entity. It has been demonstrated that SCs of the breast consistently harbour the t(12;15)ETV6-NTRK3 translocation.

The influence of basal phenotype on the metastatic pattern of breast cancer.

Aims: To assess whether basal phenotype influences the metastatic pattern and survival in patients with metastatic breast cancer.

Materials And Methods: The basal phenotype status of a well-characterised series of consecutive primary operable breast cancers (1868 cases) was ascertained using the basal cytokeratin markers CK5/6 and CK14. Follow-up data, including time, site and pattern of distant metastasis and post-metastasis survival, were available for 113 women with basal phenotype cancers and they were compared with 178 matching cases from women in the non-basal phenotype group.

CCND1 amplification and cyclin D1 expression in breast cancer and their relation with proteomic subgroups and patient outcome.

Introduction: Despite strong evidence regarding the role of CCND1 amplification and protein overexpression in breast carcinoma, the associations between CCND1 amplification/cyclin D1 overexpression and clinicopathological variables and clinical outcome remain controversial.

Aims Of The Study: (1) to correlate cyclin D1 expression with gene amplification; (2) to analyse the correlations between CCND1 amplification and overexpression with clinicopathological features and patients' outcome in invasive breast cancer; (3) to define the prevalence and clinical significance of cyclin D1 overexpression and CCND1 amplification in ER positive breast carcinomas (4) to define the prevalence of cyclin D1 overexpression and CCND1 amplification in breast cancers with basal-like immunophenotype.

Materials And Methods: CCND1 amplification and protein expression were assessed on a tissue microarray containing 880 unselected invasive breast cancer cases, by means of chromogenic in situ hybridisation using the Spotlight CCND1 amplification probe and immunohistochemistry, using the rabbit monoclonal antibody SP4.

Basal phenotype identifies a poor prognostic subgroup of breast cancer of clinical importance.

Background: Breast cancer is recognised to be a heterogeneous disease with a range of morphological appearances and behaviours. The recently recognised basal phenotype (BP) is associated with poor survival, but the clinical implications of this class of breast cancers remain to be adequately defined.

Methods: We have examined a well-characterised series of 1872 invasive breast carcinomas with a long term follow-up to assess the clinical significance of BP.

Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation.

The aim of this study was to assess the morphological characteristics and immunohistochemical profile of breast carcinomas with basal and myoepithelial phenotypes to obtain a better understanding of their biological behaviour and nature. One thousand nine hundred and forty-four invasive breast carcinomas were examined, using tissue microarray (TMA) technology and immunohistochemistry, to identify those tumours that showed basal and myoepithelial phenotypes, and their immunophenotype profile was characterized using a variety of markers. In addition, haematoxylin and eosin-stained sections of these tumours were studied for several morphological parameters.

A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes.

Amplification of 8p11-12 is a well-known alteration in human breast cancers but the driving oncogene has not been identified. We have developed a high-resolution comparative genomic hybridization array covering 8p11-12 and analysed 33 primary breast tumors, 20 primary ovarian tumors and 27 breast cancer cell lines. Expression analysis of the genes in the region was carried out by using real-time quantitative PCR and/or oligo-microarray profiling.

High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses.

Recent studies on gene molecular profiling using cDNA microarray in a relatively small series of breast cancer have identified biologically distinct groups with apparent clinical and prognostic relevance. The validation of such new taxonomies should be confirmed on larger series of cases prior to acceptance in clinical practice. The development of tissue microarray (TMA) technology provides methodology for high-throughput concomitant analyses of multiple proteins on large numbers of archival tumour samples.

High-resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry.

Loss of the chromosomal material at 16q22.1 is one of the most frequent genetic aberrations found in both lobular and low-grade nonlobular invasive carcinoma of the breast, indicating the presence of a tumour suppressor gene (TSG) at this region in these tumours. However, the TSG (s) at the 16q22.

Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma.

The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins.

Expression of the transcription factor CTCF in invasive breast cancer: a candidate gene located at 16q22.1.

CTCF is a ubiquitous 11-zinc-finger protein that plays a role in gene silencing or activation, chromatin insulation and genomic imprinting. The CTCF gene has been mapped to the chromosome band 16q22.1 that shows frequent loss of heterozygosity in breast cancer.

Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis.

Estrogen receptor (ER)-negative breast cancers are a group of tumors with poor prognosis and fewer cancer prevention and treatment strategies compared to ER-positive tumors. The aim of this study was to assess the morphological characteristics and immunohistochemical profile of ER-negative tumors and thus to understand the biological behavior and unique nature. In total, 291 consecutive ER-negative cases available from our primary breast cancer series were examined.

Expression of luminal and basal cytokeratins in human breast carcinoma.

We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray (TMA) technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any. Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and the basal markers CK 5/6 and CK 14. Additionally, assessment of alpha-smooth muscle actin (SMA) and oestrogen receptor status (ER) was performed.

Loss of CD59 expression in breast tumours correlates with poor survival.

CD59 (protectin), a phosphatidylinositol-anchored glycoprotein, is a member of the cell membrane-bound complement regulatory proteins that inhibits the formation of the terminal membrane attack complex (MAC) of complement. In this study, the expression of CD59 was evaluated in 520 breast carcinomas from patients with a mean follow-up of 87 months. This expression was correlated with clinicopathological features and patient survival.

Correlation between immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) for HER-2 in 426 breast carcinomas from 37 centres.

Accurate diagnostic assessment of HER-2 is essential for the appropriate application of the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) to the treatment of patients with metastatic breast cancer. The diagnostic test needs to be applicable to archival, fixed tissue removed at excision, in many cases several years earlier. We compared the assessment of HER-2 by immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridization (FISH) in 426 breast carcinomas from patients being considered for trastuzumab therapy.

The role of blood tumor marker measurement (using a biochemical index score and c-erbB2) in directing chemotherapy in metastatic breast cancer.

The role of blood tumor markers in monitoring response in advanced breast cancer is established in endocrine therapy and standard chemotherapy. This study examines marker levels in patients receiving new chemotherapy regimens. Thirty patients were recruited into two multicenter trials in which docetaxel-based regimens were used in 15 patients.