Invasive breast cancer following bilateral subcutaneous mastectomy in a BRCA2 mutation carrier: a case report and review of the literature

BACKGROUND: Primary prevention of breast cancer through prophylactic mastectomy can reduce the risk of malignancy in high-risk individuals. No type of mastectomy completely removes all breast tissue, but a subcutaneous mastectomy leaves more tissue in situ than does a simple mastectomy. CASE PRESENTATION: We report a case of invasive breast cancer in a BRCA2-positive woman 33 years after bilateral subcutaneous mastectomy. To our knowledge, only one case of primary breast cancer after prophylactic mastectomy in a BRCA1-positive patient has been reported in the literature and none in BRCA2-positive individuals. CONCLUSION: Careful documentation and long follow-up is essential to fully assess the benefits and risks of preventive surgical procedures in BRCA1 and BRCA2 mutation carriers

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

Isolation and partial characterization of a human pancreatic carcinoma-associated antigen defined by a novel monoclonal antibody, LD-B1

The aim of this study is to define a cellular antigen associated with human pancreatic carcinoma by developing monoclonal antibodies against the post-microsomal fraction of fresh tumor tissue. One such antibody, LD-B1, was tested by immunohistochemistry and reacted strongly with 95% of cases of pancreatic ductal carcinomas. Amongst common types of non-pancreatic malignancies, 10% were immunostained by LD-B1 and, in these cases the reaction was focal or weak. On normal pancreas, staining was observed in ductal and ductular epithelium only. The antigen was purified to homogeneity by affinity chromatography. Enzymatic and biochemical analysis showed it to be a heavily glycosylated, non-sialylated glycoprotein, that had an apparent molecular weight of 300-400 KDa. Competitive inhibition experiments indicated that it involves an extended epitope of Gal$beta1 to3$Gal$beta1 to3$(or 4)GlcNAc$beta1 to3$ Gal, which is related to blood group H antigen. An ELISA was developed and it showed elevated serum antigen levels were detected in 5 of 6 patients with pancreatic carcinoma, none of 3 patients with chronic pancreatitis, and 12 of 137 normal controls. The results indicate that patients with pancreatic carcinoma exhibit altered expression of a blood group-related antigen that can be used as a marker of pancreatic carcinoma

A real-time dashboard for managing pathology processes

Context: The Eastern Ontario Regional Laboratory Association (EORLA) is a newly established association of all the laboratory and pathology departments of Eastern Ontario that currently includes facilities from eight hospitals. All surgical specimens for EORLA are processed in one central location, the Department of Pathology and Laboratory Medicine (DPLM) at The Ottawa Hospital (TOH), where the rapid growth and influx of surgical and cytology specimens has created many challenges in ensuring the timely processing of cases and reports. Although the entire process is maintained and tracked in a clinical information system, this system lacks pre-emptive warnings that can help management address issues as they arise. Aims: Dashboard technology provides automated, real-time visual clues that could be used to alert management when a case or specimen is not being processed within predefined time frames. We describe the development of a dashboard helping pathology clinical management to make informed decisions on specimen allocation and tracking. Methods: The dashboard was designed and developed in two phases, following a prototyping approach. The first prototype of the dashboard helped monitor and manage pathology processes at the DPLM. Results: The use of this dashboard helped to uncover operational inefficiencies and contributed to an improvement of turn-around time within The Ottawa Hospital′s DPML. It also allowed the discovery of additional requirements, leading to a second prototype that provides finer-grained, real-time information about individual cases and specimens. Conclusion: We successfully developed a dashboard that enables managers to address delays and bottlenecks in specimen allocation and tracking. This support ensures that pathology reports are provided within time frame standards required for high-quality patient care. Given the importance of rapid diagnostics for a number of diseases, the use of real-time dashboards within pathology departments could contribute to improving the quality of patient care beyond EORLA′s

Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis

NRC publication: Ye