Biomedical subjects

Brian L Strauss

Publications and source records attributed to Brian L Strauss.

6 recordsLinked to original sources

PubMed2006

STAT 5a expression in the breast is maintained in secretory carcinoma, in contrast to other histologic types.

The 7 signal transducer and activator of transcription (STAT) molecules are responsible for the transcription of a variety of regulatory and differentiation proteins. STAT 5a is activated through a variety of mechanisms; in the breast, this is predominantly through binding of prolactin to its receptor. Previously, we showed that STAT 5a expression is decreased in atypical and malignant breast ductal epithelial cells. Interestingly, STAT 5a overexpression was observed in cells undergoing secretory change. In this study, secretory carcinomas were examined by immunohistochemistry for the presence of STAT 5a. In contrast to usual in situ or invasive ductal carcinoma, which lacked STAT 5a expression, all secretory carcinomas (11 invasive and 7 in situ, including 4 cases with both) expressed STAT 5a. No expression was seen in apocrine metaplasia or in other specialized breast carcinomas, such as mucinous or clear cell carcinoma. This retention of signal in the secretory carcinomas may be explained by the higher STAT 5a concentration present in cells undergoing secretory changes in general. Alternatively, STAT 5a expression may be related to the t(12;15)(p13;q25) chromosomal translocation, associated with certain pediatric tumors and recently demonstrated in many secretory carcinomas of the breast, which results in the expression of a tyrosine kinase through ETV6 and NTRK3 fusion. ETV6 also has been associated with the STAT 5a signaling pathway in another gene translocation and may be altering STAT 5a expression in secretory carcinomas. Breast cancer causes significant morbidity and mortality, and, regardless of the mechanism for retention of STAT 5a expression in this uncommon variant, the examination of STAT 5a will aid our understanding of normal and abnormal breast tissues.

Adenocarcinoma↗

PubMed2005

STAT 5a expression in various lesions of the breast.

The seven signal transducer and activator of transcription (STAT) molecules are effectors of hormonal or cytokine stimulation through receptors. STAT 5a, isolated from prolactin-stimulated mammary cells, contributes to normal proliferation and is essential for mammary gland differentiation. Using a monoclonal antibody, we tested 100 formalin-fixed, paraffin-embedded breast tissues representing everything from simple hyperplasia to invasive carcinoma for the expression of STAT 5a in comparison to normal breast epithelial cells. Immunohistochemical analysis was performed following heat treatment in a pressure cooker. STAT 5a was found in endothelial cells, adipocytes, and leukocytes as well as in the cytoplasm and nucleus of normal epithelial cells, usual ductal hyperplasia, and benign lesions such as fibroadenoma. Myoepithelial cells and stromal fibroblasts failed to demonstrate any STAT 5a in addition to most atypical proliferations including in situ and invasive carcinomas. A few examples of lobular intraepithelial neoplasia and invasive carcinoma demonstrated some reactivity, albeit comparatively reduced. The absence of STAT 5a in the abnormal breast epithelial cells may indicate a defect contributory to the abnormal state.

Breast↗

PubMed2005

cDNA expression profiling reveals elevated gene expression in cell clusters overlying focally disrupted myoepithelial cell layers: implications for breast tumor invasion.

BACKGROUND: Our previous studies revealed that a subset of mammary ductal carcinoma in situ (DCIS) contained focally disrupted myoepithelial (ME) cell layers that were predominantly overlain by estrogen receptor (ER) negative cells, which showed a substantially higher rate of cell proliferation and genetic alterations than adjacent ER positive cells within the same duct. This study attempted to assess whether these cells also had a different expression profile on tumor progression related genes. DESIGN: Consecutive sections were made from frozen tissues of 30 DCIS with focally disrupted ME cell layers and associated ER negative cell clusters. ER negative and adjacent ER positive cells within the same duct were microdissected for RNA extraction and amplification. Amplified RNA was converted to biotin-labeled cDNAs and interrogated with 'Cancer PathwayFinder' arrays. RESULTS: Cells within each or among ER negative clusters were immunohistochemically and morphologically similar, whereas they differed substantially from adjacent cells within the same duct. Of 20-paired informative ER negative and positive cells, 15 genes were differentially expressed. Of which, 11(73.3%) were higher in ER negative, 2 (13.3%) were higher in ER positive, and 2 (13.3%) were equal in these cells (p <0.01). Of 11 up-regulated genes in ER negative cells, 8 indirectly or directly promote proliferation and progression, and 3 promote apoptosis. CONCLUSION: ER negative cell clusters showed a significantly higher expressing frequency of multiple tumor progression related genes than their adjacent ER positive counterparts, suggesting that they are likely to be biologically more aggressive and have a greater potential for invasion.

Breast Neoplasms↗

PubMed2004

Direct and repeat uses of tissue sections as templates for liquid-phase polymerase chain reaction amplification: applications and implications.

The liquid-phase polymerase chain reaction (PCR) technique is the most commonly used method for the amplification of genetic materials, although it requires the lysis of cells for DNA or RNA extraction, making it impossible to visualize the distribution and subcellular localization of the biomolecules. This study intended to assess whether tissue sections may be directly and repeatedly used as templates for liquid-phase PCR amplifications. Consecutive paraffin sections of breast tissues were placed on gamma-methacryloxypropyltrimethoxysilane-coated microscopic cover glasses perforated with a diamond knife into strips. After hematoxylin and eosin or immuno-staining, the strip of interest was inserted into a PCR tube for amplifications, and the adjacent strip with the same tissue was subject to microdissection, DNA extraction, and PCR amplifications. To use the strip repeatedly, it was transferred into a new PCR tube and amplified with a new primer set, after an initial amplification for 5 to 7 cycles. Then, initially amplified samples were amplified to a total of 40 cycles. An equal volume of PCR products from the strip and DNA extract were loaded side by side for electrophoresis and detection. The strip and DNA extract from the same tissue yielded a very comparable quality and quantity of PCR products with the same primer sets. The strip, however, could be repeatedly used for PCR amplifications with substantially more primer sets. In addition, the strip could be used for immunohistochemical or other molecular assays after PCR amplifications. Further studies with the same protocol on strips containing chromosomal spreads generated similar results.

DNA↗

PubMed2004

Immunohistochemical staining for Ki-67 and p53 helps distinguish endometrial Arias-Stella reaction from high-grade carcinoma, including clear cell carcinoma.

The distinction of the Arias-Stella reaction from clear cell carcinoma of the endometrium is usually straightforward; however, this differential diagnosis can be difficult when the Arias-Stella reaction occurs outside the setting of pregnancy or in older patients. The differential diagnosis also is problematic when serous or clear cell carcinoma focally arises within an endometrial polyp, as part of "endometrial intra-epithelial carcinoma" (EIC), or in younger patients. The goal of this study was to determine whether immunohistochemical staining can distinguish the Arias-Stella reaction from endometrial high-grade carcinoma, particularly clear cell carcinoma. Cases of endometrial Arias-Stella reaction (n = 27), clear cell carcinoma (n = 11), serous carcinoma (n = 7), and EIC (n = 4) were assessed by immunohistochemical staining with antibodies for Ki-67, p53, estrogen receptor (ER), and progesterone receptor (PR). Composite immunohistochemical scores based on the percentage and intensity of stained cells were calculated, as was the overall positivity (percentage positive cases), using a cutoff value of >/=5% stained cells and at least weak intensity. Appropriate statistical tests were performed. Ki-67 and p53 immunostaining was significantly less in Arias-Stella reaction than in clear cell carcinoma (p < 0.0001 for both) or serous carcinoma/EIC (p < 0.0001 for both), measured by the composite immunohistochemical scores or overall positivity. ER showed a significant difference only between Arias-Stella reaction and clear cell carcinoma; PR showed a significant difference only between Arias-Stella reaction and serous carcinoma/EIC. When clinical or histologic features cannot facilitate the differential diagnosis, immunohistochemical staining for Ki-67 and p53 may help distinguish endometrial Arias-Stella reaction from clear cell carcinoma and other types of high-grade carcinoma.

Adenocarcinoma, Clear Cell↗

PubMed2003

Cell clusters overlying focally disrupted mammary myoepithelial cell layers and adjacent cells within the same duct display different immunohistochemical and genetic features: implications for tumor progression and invasion.

INTRODUCTION: Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale. METHODS: Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by > or = 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability. RESULTS: Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers. CONCLUSIONS: Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation of a biologically more aggressive cell clone and the myoepithelial cell layer breakdown possibly associated with tumor progression or invasion.

Breast↗