Faculty Bibliography

The co-existence of breast and ovarian cancers in the same individual should raise suspicion of a hereditary process. Patients with either BRCA1 or BRCA2 germ-line mutations have an average risk of 39% and 11% respectively of developing ovarian cancer by the age of 70; they have a risk of 35-85% of developing breast cancer in their lifetime. We report here unusual pathologic features in a BRCA2 germ-line mutation carrier recently diagnosed with synchronous breast and ovarian cancers, and summarize the findings in six other women who were diagnosed with ovarian cancer either simultaneously with the diagnosis of breast cancer or at varying times after the diagnosis. While in most instances this may be a coincidental occurrence in highly susceptible individuals, the patient we highlight raises the provocative hypothesis that at times breast cancer metastasizes to the ovaries of mutation carriers and stimulates the development of an ovarian cancer as well as other cancers. In addition, these ovarian cancers may have different mechanisms of metastases predisposing them to travel to unusual sites

Lymphovascular invasion (LVI) of breast cancer is an independent adverse prognosticator that is associated with increased regional and distant tumor recurrence. LVI is infrequently encountered in invasive lobular carcinoma when compared to invasive ductal carcinoma. We employed D2-40 antibody, a novel marker for lymphatic endothelial cells, in an attempt to enhance the detection of LVI in invasive lobular carcinomas. We identified 78 patients with invasive lobular carcinoma with known axillary status, who were studied between 2003 and 2006. D2-40 antibody was applied to one representative paraffin block from each case and the results were compared to LVI on routine histology. LVI was identified in 12 (15%) and 19 (24%) cases by routine histology and D2-40 antibody, respectively. Eleven of 12 patients (92%) with LVI identified by routine histology had axillary nodal metastasis compared to 14 of 19 patients (74%) with LVI identified by D2-40 antibody. LVI was missed by routine histology in 8 cases (10%). D2-40 antibody enhanced the identification of LVI by 9% in node negative patients. D2-40 antibody increased the identification of LVI by 12% in classic invasive lobular carcinoma. In conclusion, D2-40 antibody staining may be useful as an adjunct in detecting LVI in invasive lobular carcinoma, especially in node-negative patients with the classic variant of invasive lobular carcinoma

INTRODUCTION: With the adoption of routine screening mammography, breast cancers are being diagnosed at earlier stages, with DCIS now accouting for 22.5% of all newly diagnosed breast cancers. This has been attributed to both increased breast cancer awareness and improvements in breast imaging techniques. How have these changes, including the increased use of image-guided sampling techniques, influenced the clinical practice of breast surgery? METHODS: The institutional pathology database was queried for all breast surgeries, including breast reconstruction, performed in 1995 and 2005. Cosmetic procedures were excluded. The results were analysed utilizing the Chi-square test. RESULTS: Surgical indications changed during 10-year study period, with an increase in preoperatively diagnosed cancers undergoing definitive surgical management. ADH, and to a lesser extent, ALH, became indications for surgical excision. Fewer surgical biopsies were performed for indeterminate abnormalities on breast imaging, due to the introduction of stereotactic large core biopsy. While the rate of benign breast biopsies remained constant, there was a higher percentage of precancerous and DCIS cases in 2005. The overall rate of mastectomy decreased from 36.8% in 1995 to 14.5% in 2005. With the increase in sentinel node procedures, the rate of ALND dropped from 18.3% to 13.7%. Accompanying the increased recognition of early-stage cancers, the rate of positive ALND also decreased, from 43.3% to 25.0%. CONCLUSIONS: While the rate of benign breast biopsies has remained constant over a recent 10-year period, fewer diagnostic surgical image-guided biopsies were performed in 2005. A greater percentage of patients with breast cancer or preinvasive disease have these diagnoses determined before surgery. More preinvasive and Stage 0 cancers are undergoing surgical management. Earlier stage invasive cancers are being detected, reflected by the lower incidence of axillary nodal metastases

Translational regulation is critical in cancer development and progression. Translation sustains tumor growth and development of a tumor vasculature, a process known as angiogenesis, which is activated by hypoxia. Here we first demonstrate that a majority of large advanced breast cancers overexpress translation regulatory protein 4E-BP1 and initiation factor eIF4G. Using model animal and cell studies, we then show that overexpressed 4E-BP1 and eIF4G orchestrate a hypoxia-activated switch from cap-dependent to cap-independent mRNA translation that promotes increased tumor angiogenesis and growth at the level of selective mRNA translation. Elevated levels of 4E-BP1 trigger hypoxia inhibition of cap-dependent mRNA translation at high-oxygen levels and, with eIF4G, increase selective translation of mRNAs containing internal ribosome entry sites (IRESs) that include key proangiogenic, hypoxia, and survival mRNAs. The switch from cap-dependent to cap-independent mRNA translation facilitates tumor angiogenesis and hypoxia responses in animal models

Benign adenomyoepithelioma of the breast is a rare tumor in which the cytologic findings have been described in only a few cases. While benign, the imaging and pathologic features may be mistaken for malignancy. We report the aspiration biopsy findings in four cases of adenomyoepithelioma with radiologic and histologic correlation. Cytopathologists should familiarize themselves with this entity to avoid a misdiagnosis of carcinoma

Objective: While the use of fine needle aspiration (FNA) in the diagnosis of gastrointestinal stromal tumours (GISTs) is well-established, it can be difficult to predict the prognosis of GIST based on morphology alone. The objective of the current study was to determine if expression of bcl-2, Ki-67 and p53 correlated with the outcome of GISTs based on cytological material. Methods: Cell-blocks from 14 GISTs diagnosed by FNA were retrieved. Immunostaining was performed with antibodies against bcl-2, Ki-67 and p53. All cytological diagnoses were confirmed by positive immunostaining with c-kit and/or subsequent histological evaluation. Positivity for bcl-2, Ki-67 and p53 was defined as the presence of >= 10% cytoplasmic staining, >= 5% nuclear staining and >= 5% nuclear staining respectively. Results: The 14 patients consisted of seven males and seven females with a mean age of 58 years. The average follow-up interval was 46 months. Six had a benign course and eight developed recurrences/metastases. Thirteen (93%) cases showed positive staining for bcl-2. Positive Ki-67 and p53 staining was noted in one (7%) and seven (50%) cases respectively. The difference in staining for p53 between aggressive and non-aggressive GISTs was statistically significant. No statistically significant difference was noted for bcl-2 staining or Ki-67 labelling index between the two groups. Conclusions: According to our observations, p53 immunostaining may be useful in predicting the outcome of GIST diagnosed by FNA; Ki-67 and bcl-2 are not useful as prognostic markers for GIST in FNA specimens