Profiles of brain metastases: prioritization of therapeutic targets

We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of nonsmall cell lung cancer, breast cancer and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (assayed by immunohistochemistry) and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification and mutations among brain metastases, extracranial metastases and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8,178 nonsmall cell lung cancers (5,098 primaries; 2,787 systemic metastases; 293 brain metastases), 7,064 breast cancers (3,496 primaries; 3,469 systemic metastases; 99 brain metastases) and 1,757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1 and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication and/or repair

Myoepithelial cells: good fences make good neighbors

The mammary gland consists of an extensively branched ductal network contained within a distinctive basement membrane and encompassed by a stromal compartment. During lactation, production of milk depends on the action of the two epithelial cell types that make up the ductal network: luminal cells, which secrete the milk components into the ductal lumen; and myoepithelial cells, which contract to aid in the ejection of milk. There is increasing evidence that the myoepithelial cells also play a key role in the organizational development of the mammary gland, and that the loss and/or change of myoepithelial cell function is a key step in the development of breast cancer. In this review we briefly address the characteristics of breast myoepithelial cells from human breast and mouse mammary gland, how they function in normal mammary gland development, and their recently appreciated role in tumor suppression

P-cadherin expression in breast cancer: a review

P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumour aggressiveness. In addition, expression of P-cadherin is well established as an indicator of poor prognosis in human breast cancer, which has stimulated our interest in studying its role in this setting. This review describes the most important findings on P-cadherin expression and function in normal mammary tissue and breast cancer cells, emphasizing that further research is required to elucidate the role played by this protein in human mammary tumours

Adenomyoepithelioma of the breast: A proposal for classification

Breast lesions with a prominent myoepithelial cell component constitute a heterogeneous group of benign and malignant neoplastic proliferations. These lesions are often dual epithelial‐myoepithelial but may be purely myoepithelial cell in nature. Benign epithelial‐myoepithelial lesions typically maintain the morphology and immunophenotype of the normal bilayer epithelial myoepithelial structures. However, the distinction between the two cell components is not always clear‐cut in malignant lesions in which the histogenesis of myoepithelial cells remains uncertain. Neoplastic biphasic epithelial‐myoepithelial lesions of the breast include adenomyoepithelioma (AME), pleomorphic adenoma and adenoid cystic carcinoma. Four histological patterns of classical AME have been described: tubular, lobulated, spindle cell and adenosis variants. Overlapping patterns occur and some AMEs display an intraductal papillary pattern that may represent a fifth variant. AME can be benign or malignant. Classical AME may show atypical features, which are not sufficient for the diagnosis of malignancy (atypical AME). Atypical AME is recognised as a lesion of uncertain malignant potential with limited metastatic capability. Based on the histological features, we propose a classification of malignant AME (M‐AME) into three variants: M‐AME in situ, M‐AME invasive and AME with invasive carcinoma. In this review, we provide an overview of myoepithelial lesions of the breast focusing on the classification of AME to improve not only the consistency of reporting but also help guide further management decision making

Seeking Asylum

This submission won first place in the 2020 Images of Research competition. The competition celebrates undergraduate contributions to research at the University of Texas. The following caption accompanied the image submission: The Migrant Protection Protocols require asylum applicants to remain in Mexico while awaiting court proceedings. Only a certain number of people are processed at each port of entry per day, so the rest are turned back and given a number on a ‘list’. These asylum seekers have set up camps like this one in Matamoros where they wait months to present their claims for asylum. In this camp, entities from the U.S. provide shelter, limited food and healthcare, legal counsel and education to migrants. The camp is roughly divided by nationality and each group has de-facto leaders.We visited three cities in Mexico in January and uncovered allegations that some Mexican officials had accepted bribes to advance migrants’ names on the list. We also found that Mexican citizens claiming asylum were being queued and sent back to Mexico–a possible contravention of the ‘non-refoulment’ doctrine that forbids a country from returning asylum seekers to a country where they could face persecution.We have shown our findings to attorneys, human rights advocates and university faculty.Ostrow, MicheleUT Librarie