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We have conducted proteome-wide analysis of fresh surgery specimens derived from breast cancer patients, using an approach that integrates size-based intact protein fractionation, nanoscale liquid separation of peptides, electrospray ion trap mass spectrometry, and bioinformatics. Through this approach, we have acquired a large amount of peptide fragmentation spectra from size-resolved fractions of the proteomes of several breast tumors, tissue peripheral to the tumor, and samples from patients undergoing noncancer surgery. Label-free quantitation was used to generate protein abundance maps for each proteome and perform comparative analyses. The mass spectrometry data revealed distinct qualitative and quantitative patterns distinguishing the tumors from healthy tissue as well as differences between metastatic and non-metastatic human breast cancers including many established and potential novel candidate protein biomarkers. Selected proteins were evaluated by Western blotting using tumors grouped according to histological grade, size, and receptor expression but differing in nodal status. Immunohistochemical analysis of a wide panel of breast tumors was conducted to assess expression in different types of breast cancers and the cellular distribution of the candidate proteins. These experiments provided further insights and an independent validation of the data obtained by mass spectrometry and revealed the potential of this approach for establishing multimodal markers for early metastasis, therapy outcomes, prognosis, and diagnosis in the future.

The γ subunit of the major histocompatibility complex (MHC) class II complex, CD74, is overexpressed in a significant proportion of metastatic breast tumors, but the mechanistic foundation and biologic significance of this phenomenon are not fully understood. Here, we show that when CD74 is overexpressed in human cancer and noncancerous epithelial cells, it interacts and interferes with the function of Scribble, a product of a well-known tumor suppressor gene. Furthermore, using epithelial cell lines expressing CD74 under the control of tetracycline-inducible promoter and quantitative high-resolution mass spectrometry, we demonstrate that, as a result of CD74 overexpression, the phosphorylation pattern of the C-terminal part of Scribble undergoes specific changes. This is accompanied with a translocation of the protein from the sites of cell-to-cell contacts at the plasma membrane to the cytoplasm, which is likely to effectively enhance the motility and invasiveness of the cancer cells.

Diagnostic dilemma while dealing with a suspected breast cancer is not rare. Involvement of multidisciplinary team as well as patient is important in the decision-making. The report illustrates a rare presentation of a deep seated large epidermoid cyst of breast, which mimicked carcinoma, caused diagnostic confusion and entailed mastectomy. We strongly advocate the option of breast reconstruction in such cases.

We report on a case of metastatic Merkel cell carcinoma in a 74-year-old patient with positive staining for thyroid transcription factor-1. This represents a new immunohistochemical staining pattern for Merkel cell carcinoma and has implications regarding the accurate diagnosis of this tumor type.

Primary cutaneous extraskeletal osteosarcoma (PCEO) is a rare malignant neoplasm with less than 20 cases reported in the literature to date. Presenting as a nodule or mass on the skin, commonly at sites of previous trauma or radiation, these lesions are differentiated from other neoplasms through their characteristic microscopic appearance. This report highlights a case of PCEO in a 75-year-old man with a history of squamous cell carcinoma (SCC) of the scalp. Histological examination of a scalp nodule in the region of a previously excised SCC revealed proliferation of osteoid surrounded by malignant osteocytes. An overview of this condition and differential diagnoses are presented in this report.

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not available at time of publication. Abstract not available at time of publication. Retrospective studies on male breast cancer (MBC) have suff ered from small numbers of cases available from any one centre; thus a signifi cant problem in eff ectively studying this disease is accruing suffi ciently large numbers to allow comparative analysis of biomarkers associated with response. Using a coordinated multicentre approach, we present the fi rst large-scale study to address the relevance of the expression of hormone receptors in MBC and female breast cancer (FBC) using immunohistochemistry combined with a novel bioinformatics approach. Following ethical approval, 523 archival blocks (260 MBCs and 263 matched FBCs) were obtained retrospectively. Tissue microarrays were constructed and sections stained for ERα, ERβ1, ERβ2, ERβ5, total PR, PRA, PRB and AR and typed using CK5/6, CK14, CK18 and CK19 by immunohistochemistry. Following scoring, a range of ordination techniques were conducted on the datasets including hierarchical clustering and principal component analysis (PCA) + ) were infrequent in both. Hierarchical clustering revealed common clusters between MBC and FBC including total PR-PRA-PRB and ERβ1/2 clusters. ERα occurred on distinct clusters between males and females. AR, ERβ1, ERβ2 and ERβ5 all existed on the same cluster but with a diff erent substructure, particularly around the positioning of AR. ERα associated with this cluster in the male but not the female group. PCA confi rmed that in both groups strong infl uences came from PR-PRA-PRB. In MBC strong infl uences additionally came from AR and ERβ1, ERβ2 and ERβ5, whereas in FBC strong infl uences came from ERα alone. Our data support the hypothesis that breast cancer is biologically diff erent in male and females, which could have implications for therapy. Introduction The response rarely sustains long among the responders for Herceptin (trastuzumab) monotherapy treatment. It is still poorly understood how Herceptin exerts its mechanism of action and how the acquired resistance to this drug occurs. Materials and methods We used a multidisciplinary approach including fl uorescence resonance energy transfer and biochemical methods to assess the eff ects of Herceptin on various signalling pathways and to determine the acquired resistance mechanisms of Herceptin in various HER2-positive breast cell lines and a BT474 xenograft model. Results We have shown that Herceptin does not decrease HER2 phosphorylation despite the eff ect on HER2 receptor downregulation. HER2 phosphorylation is maintained by the activation of EGFR, HER3 and HER4 via their dimerisation with HER2 in breast cancer cells. The activation of EGFR, HER3 and HER4 is induced by HER ligand release, including heregulin and betacellulin. The release of HER ligands is mediated by ADAM proteases including ADAM17/TACE. Furthermore, we demonstrated that the feedback loop involving HER ligands and ADAM proteases is activated due to a decrease in PKB phosphorylation induced by Herceptin t...