ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

INTRODUCTION: Bone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. METHODS: To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene-expression profiles from laser-capture microdissected trephine biopsies of both breast cancer bone metastases and independent primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared with primary, bone-metastatic breast tumors. RESULTS: ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary breast tumors. In addition, ABCC5 was significantly upregulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 substantially reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers in vivo. Finally, conditioned media from breast cancer cells with reduced ABCC5 expression failed to induce in vitro osteoclastogenesis to the same extent as conditioned media from breast cancer cells expressing ABCC5. CONCLUSIONS: Our data suggest that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for efficient osteoclast-mediated bone resorption. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis

Gene expression signatures of morphologically normal breast tissue identify basal-like tumors

INTRODUCTION: The role of the cellular microenvironment in breast tumorigenesis has become an important research area. However, little is known about gene expression in histologically normal tissue adjacent to breast tumor, if this is influenced by the tumor, and how this compares with non-tumor-bearing breast tissue. METHODS: To address this, we have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty (n = 44). RESULTS: Based on this data, we determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumor-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumor tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favorable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis. CONCLUSION: Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression dataset for comparative studies of tumor expression profiles

Ovarian Mixed Malignant Brenner-Mucinous Tumor with Signet Ring Cells

Mucinous carcinomas with signet ring cells in the ovary, particularly those composed predominantly of signet ring cells, are extremely rare, and in vast majority of cases, they represent metastasis from another site such as the stomach, appendix, pancreaticobiliary tract, bladder, and breast (Hristov et al., 2007, Kiyokawa et al., 2006, Vang et al., 2006, Young, 2006). Malignant Brenner tumor is also rare comprising less than 0.5% of ovarian carcinoma. Although mixed Brenner-Mucinous tumors are relatively common, the combination of a primary ovarian signet ring carcinoma with a malignant Brenner tumor is unique and to the best of our knowledge not previously reported in the literature

Epithelial-Myoepithelial Carcinoma of the Breast with Rhabdoid Features

Epithelial-myoepithelial carcinoma of the breast is a rare biphasic tumor composed of intermixed malignant epithelial and myoepithelial components. Myoepithelial cells are known to adopt varied morphologies, including spindle, chondroid, clear cell, and rhabdoid morphologies, and can represent a diagnostic challenge when isolated on biopsy. Rhabdomyosarcoma, phyllodes tumor, metaplastic carcinoma, and myoepithelial carcinoma are primary breast tumors that all have been shown to exhibit rhabdoid features, whether representing true differentiation or morphological mimic. We here report an epithelial-myoepithelial carcinoma of the breast with rhabdoid features in a 76-year-old woman. The rhabdoid-appearing myoepithelial cells are negative for myogenin, consistent with a rhabdoid-like morphology rather than a true rhabdoid differentiation, comparably to previously described myoepithelial carcinoma with rhabdoid features. To our knowledge, this is the first reported case of epithelial-myoepithelial carcinoma of the breast with rhabdoid features and thus adds another entity to the differential diagnosis of breast lesions with rhabdoid features

Right Atrial Hydatid Cyst Prolapsing into the Tricuspid Valve

WOS: 000225746300026PubMed: 15745306

Axillary Metastasis from an Occult Tubal Serous Carcinoma in a Patient with Ipsilateral Breast Carcinoma: A Potential Diagnostic Pitfall

Axillary nodal metastasis from a nonmammary neoplasia is much rarer than diseases associated with a primary breast carcinoma. However, this has to be considered in the differential diagnosis of nodal disease in patients with a history of breast cancer. Here, we report the case of a 73-year-old female with a past medical history of breast cancer, presenting with an ipsilateral axillary metastatic carcinoma. The immunohistochemical profile of the metastatic lesion was consistent with a high grade serous carcinoma. After undergoing a total abdominal hysterectomy and salpingo-oophorectomy, thorough pathological examination revealed two microscopic foci of serous carcinoma in the right fallopian tube, not detectable by preoperative magnetic resonance imaging. In this context, the poorly differentiated appearance of the metastatic tumor and positive staining for estrogen receptor, might lead to a misdiagnosis of metastatic breast carcinoma. As the therapeutic implications differ, it is important for the pathologist to critically assess axillary lymph node metastases, even in patients with a past history of ipsilateral breast carcinoma and no other known primary tumors