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Biomedical subjects

V Speirs

Publications and source records attributed to V Speirs.

At least 19 recordsLinked to original sources
PubMed2006

Properties and characteristics of the dyes injected to assist axillary sentinel node localization in breast surgery.

AIMS: A review of the safety profile of dyes injected to assist in sentinel lymph node biopsy (SLNB) in breast cancer. METHODS: A literature search was performed of the medline database 1966-2005 using the Ovid web Gateway detailing the words sentinel node, breast cancer, allergic reactions, blue dye, isosulfan blue, patent blue and methylene blue. RESULTS: There are reported side-effects from the parenteral administration of dyes, which range from minor to life threatening in severity. There are differences between the dyes as regards their effects. These aspects are discussed. CONCLUSION: Many dyes have been used for SLNB with acceptable identification rates. There are variable side-effects for each of those dyes. Further research is needed to clarify the safety profile of these dyes.

Axilla↗
PubMed2005

Steroid hormone receptor expression in male breast cancer.

AIMS: To investigate expression of the steroid hormone receptors estrogen receptor (ER)-alpha and -beta, progesterone receptor (PR) and androgen receptor (AR) in male breast cancer. METHODS: Specimens from 16 male breast cancers were immunostained for ERalpha, ERbeta, PR and AR. FINDINGS: Eighty-seven percent of tumours expressed ERalpha, 93% PR, 87% ERbeta and 87% AR. Staining for ERalpha and PR was confined exclusively to the nuclei of epithelial cells with some heterogeneity. Nuclear immunoreactivity was also observed with AR. Again this was restricted to epithelial cells but tended to be more uniform. ERbeta was seen in the nuclei of epithelial cells and also in stromal fibroblasts and lymphocytes. Analysis of serial sections revealed a similar pattern of staining with ERbeta and AR in epithelial cells. CONCLUSIONS: In addition to expression of the better known steroid receptors, ERalpha, PR and AR, we have demonstrated a high rate of expression of ERbeta in male breast cancer. This is in keeping with the generally high steroid receptor expression seen in males. However, the abundance of ERbeta expressed in this small series of male breast cancer is in contrast to female breast cancer where ERbeta expression is often reduced.

Biomarkers, Tumor↗
PubMed2005

Expression of prostate specific antigen in male breast cancer.

Male breast cancer is uncommon, accounting for less than 1% of all breast cancers. Carcinoma metastatic to the male breast is also unusual, with metastatic prostatic carcinoma being among the most common primary sites from which such tumours derive. Metastatic prostatic cancer and primary breast cancer may be histologically indistinguishable without immunohistochemistry because both often infiltrate with a cribriform architecture. Distinguishing between primary and metastatic disease within the breast is important because the treatment options for each are radically different. Following a case in which metastatic prostatic disease was initially wrongly diagnosed as primary breast cancer, a small series of male breast cancers was examined for expression of prostate specific antigen (PSA) and prostatic acid phosphatase to assess the usefulness of these markers in making this distinction. Focal expression of PSA was found in one of 11 cases of male breast cancer. These results indicate that PSA should be used with caution in this context.

Aged↗
PubMed2005

Angiogenesis in breast cancer: how should we measure this? (Review).

Despite the established importance of angiogenesis in the pathogenesis of solid tumours, there is still no consensus on how this is best measured or which method is the most appropriate in the determination of prognosis. Here we review the pros and cons of current methods of assessing angiogenesis, both clinical and in the laboratory, and discuss with respect to breast cancer.

Breast Neoplasms↗
PubMed2005

Loss of expression of oestrogen receptor beta in colon cancer and its association with Dukes' staging.

Gender differences in the incidence and behaviour of colon cancer suggest a hormonal influence and epidemiological data suggest a protective effect for hormone replacement therapy. Recently, it has been shown that oestrogen receptor (ER) beta is the predominant ER in colon tissue. The aim of this study was to examine the expression and distribution of ERbeta in normal and colorectal cancer samples, using immunohistochemistry and (in a subset of patients) real-time quantitative reverse transcriptase polymerase chain reaction in a well-defined patient cohort and to correlate this with clinico-pathological outcome. Immunohistochemical analyses of normal colon revealed strong specific nuclear immuno-reactivity in all epithelial cells lining the colonic crypts. In colon cancer, ERbeta expression was lost in 21% of samples irrespective of patient age or gender. Interestingly loss of ERbeta expression was higher in left colon and rectal cancers (27%) compared to right colon cancers (8%). A correlation between loss of ERbeta expression and advanced Dukes stage was observed. Loss of ERbeta with increased Dukes' stage suggests that it may be affording a protective effect against colon carcinogenesis. Its presence may be a favourable prognostic marker in this disease and could explain the protective effect of oestrogens against colon cancer development.

Aged↗
PubMed2004

Tissue microarrays--big potential from small samples (review).

For well over a century, pathologists have used formalin-fixed paraffin-embedded tissues for microscopic examination and subsequent diagnosis of human disease. However, this type of approach is usually limited to the analysis and/or detection of one or two specific features on a single slide from an individual section. This area of histological study has been revolutionised by the development of tissue microarrays (TMAs). This review describes the development and use of TMAs and discusses their possible applications to clinical oncological practice.

Breast Neoplasms↗
PubMed2002

Evaluation of seven oestrogen receptor beta antibodies for immunohistochemistry, western blotting, and flow cytometry in human breast tissue.

Two oestrogen receptors, ER alpha and ER beta, exist. While much is known about ER alpha, the role of ER beta is still undefined, especially at the protein level. The aim of this study was to determine the utility of seven ER beta antibodies (14C8, 8D5, PAI313, PPG5/10, N19, 9.88, and D7N) raised against different domains of ER beta in three commonly used laboratory applications, namely immunohistochemistry, western blot, and flow cytometry, using human breast material. For immunohistochemical analysis of frozen material, PAI313 and D7N gave stronger and more specific signals than 14C8, 8D5, and PPG5/10. In paraffin sections, 14C8, closely followed by PPG5/10, gave by far the most superior nuclear immunoreactivity, compared with the other antibodies tested. In general, flow cytometry results mirrored the immunohistochemistry data for paraffin sections, with antibodies ranked 14C8 > 8D5> or = PAI-313 > PPG5/10 >D7N. For western blotting, 8D5 and D7N yielded the strongest and most consistent bands, with weaker bands seen with the others. It is concluded that ER beta protein can be detected using specific antibodies. However, there is considerable variation between the specificity and application of these antibodies, highlighting the fact that careful optimization is required when selecting an antibody for use in a particular laboratory technique.

Antibodies, Monoclonal↗
PubMed2002

Distinct expression patterns of ER alpha and ER beta in normal human mammary gland.

AIM: Two oestrogen receptors (ERs) have been identified to date-the "classic" ER alpha and the more recently described ER beta. Although much is known about ER alpha at the mRNA and protein levels, our knowledge of the expression and distribution of ER beta protein is much more limited. The aim of this study was to compare the cellular distribution of ER alpha and ER beta in normal human mammary gland. METHODS: Formalin fixed, paraffin wax embedded material was obtained from reduction mammoplasty specimens, normal tissue adjacent to breast tumour, or fibroadenoma. Sections were immunohistochemically stained for ER alpha, ER beta, and the progesterone receptor. The staining pattern for each antibody was evaluated and compared. RESULTS: ER alpha was restricted to the cell nuclei of epithelial cells lining ducts and lobules. Although ER beta was also seen in these cells, additional strong staining was detected specifically in the cell nuclei of myoepithelial cells. Occasional staining was seen in surrounding stromal and endothelial cell nuclei and in lymphocytes. CONCLUSIONS: ER subtypes have distinct distribution patterns in the normal mammary gland. The widespread distribution of ER beta suggests that it may be the dominant ER in the mammary gland where it may be acting as a natural suppressor.

Breast↗
PubMed2001

Genetic events during the transformation of a tamoxifen-sensitive human breast cancer cell line into a drug-resistant clone.

Tamoxifen resistance is a serious clinical problem commonly encountered in the management of patients with breast cancer. The mechanisms leading to its development are unclear. Tamoxifen acts via multiple pathways and has diverse effects. Hence transformation from a tamoxifen-sensitive to a resistant phenotype could involve multiple genetic events. Knowledge of the genetic pathways leading to resistance may facilitate the development of novel therapeutic strategies. In this study, a variation of conventional comparative genomic hybridization (CGH) has been employed to detect genetic alterations associated with tamoxifen resistance. MCF-7, a tamoxifen-sensitive human breast cancer cells line, and its tamoxifen-resistant clone, CL-9 were used. Both cell lines showed extensive areas of concordance but consistent differences were seen with the acquisition of tamoxifen resistance. These differences included the amplification of 2p16.3 approximately p23.2, 2q21 approximately q34, 3p12.3 approximately p14.1, 3p22 approximately p26, 3q, 12q13.2 approximately q22, 13q12 approximately q14, 17q21.3 approximately q23, 20q11.2 approximately q13.1 and 21q11.2 approximately q21 as well as the deletion of 6p21.1, 6p23 approximately p25, 7q11.1 approximately q31, 7q35 approximately q36, 11p15, 11q24, 13q33, 17p, 18q12 approximately q21.1, 19p, 19q13.3, 22q13.1 approximately q13.2. These findings were supported by conventional cytogenetics and chromosome painting. The regions identified by CGH potentially harbor genes that could be important in the development of tamoxifen resistance.

Antineoplastic Agents, Hormonal↗
PubMed2001

Expression of alternatively spliced estrogen receptor alpha mRNAs is increased in breast cancer tissues.

We previously identified 20 different alternatively spliced estrogen receptor alpha (ERalpha) mRNAs that have deletions in various combinations of exons in breast cancer cell lines using a novel 'Splice Targeted Approach' [J. Steroid Biochem. Mol. Biol. 72 (2000) 249]. In the current study, we compared the frequency of alternatively spliced ERalpha variant expression in 35 reduction mammoplasty and 38 breast cancer tissues with known ERalpha, ERbeta status using this highly specific 'Splice Targeted Approach'. A total of 16 different alternatively spliced variants were identified that have deletions in various combinations of exons in normal, as well as cancer tissues. However, not all 16 variants were present in every tissue. The frequency and type of variants in normal and cancer tissues was significantly different. Majority of normal tissues expressed only single exon deletion variants with the exception of those in combination with exon 2Delta and 7Delta. Tumor tissues, on the other hand, showed increased frequency of multiple exon deletion mRNAs (P<0.019). In addition, cancer tissues also showed an increased frequency of all variants compared with normal tissues (P<0.044). Among the 16 variants, the dominant negative variant, exon 3Delta, showed the most significant increase in cancer tissues (P=0.000032). Specifically, we detected four different mRNAs that have exon 2 deletion-exon 2Delta; 2 and 4Delta; 2 and 5Delta; and 2, 4-5Delta in various combinations in both normal and cancer tissues. A large number of normal tissues expressed two transcripts-exon 2Delta and 2, 4-5Delta. The multiple exon deletion 2, 4-5Delta were predominant in cancer tissues. Only the single exon 3 deletion variant, exon 3Delta, was detected in normal tissues. Cancer tissues showed the presence of a double exon deletion variant, exons 3 and 7Delta, in addition to exon 3Delta. A small fraction of normal tissues showed exons 2-3Delta mRNAs, whereas, cancer tissues showed increased frequency of exons 2-3Delta expression in addition to a triple exon deletion variant, exons 2-3, and 5Delta. The expression of exon 4Delta; or 4 and 7Delta or both was equivalent in normal and cancer tissues. Exon 5Delta transcripts were present at very low levels in both normal and tumor tissues. A small percentage of cancer tissues but not normal tissues showed exon 6Delta mRNA. The presence of single, double, triple and quadruple exon deletion mRNAs, exon 7Delta; 7 and 4Delta; 7, 3-4Delta; 7, 3-5Delta, respectively, were detected in normal as well as cancer tissues. Each normal and cancer tissue had a distinct profile of ERalpha wild type, ERbeta wild type and ERalpha splice variants. Heterogeneity in ER isoform profiles may result in variations in estrogen/anti-estrogen binding and activation/inactivation of estrogen-dependent genes, and, therefore, may have implications in the risk of developing breast cancer, survival with the disease and response to anti-estrogen, as well as other therapies.

Alternative Splicing↗
PubMed2000

Genetic changes in breast cancer detected by comparative genomic hybridisation.

Breast cancer is characterised by a number of genetic aberrations. Our purpose was to use comparative genomic hybridisation (CGH) to screen breast carcinomas for copy number changes: 44 ductal and 8 lobular carcinomas were studied and a large number of genetic aberrations identified. Many of these showed similarity to previous CGH results, however, a number of loci not previously shown to have undergone frequent change were identified. This included copy number gains affecting chromosomes 1p, 4q, 5q, 6q and 13q. Furthermore, we have identified 2 regions of copy number change, the gain on 5p and deletion of 16q, which correlated with lobular carcinomas. Our results highlight several areas of the genome that may be important in the molecular genetics of breast cancer.

Adult↗
PubMed2000

Prognostic significance of oestrogen receptor beta in breast cancer.

BACKGROUND: Endocrine therapy for breast cancer is now well established and with the identification of a second oestrogen receptor, ERbeta, 3 years ago it is timely to review the possible significance of this receptor in breast cancer management. METHODS: An up-to-date review of the current literature concerning the role and possible implications of ERbeta in human breast cancer was undertaken. RESULTS: Wild-type and variant ERbeta are expressed in human breast tumours. Expression of ERbeta correlates with accepted prognostic indicators including lymph node status and tumour grade. Furthermore, levels of ERbeta messenger RNA alter during carcinogenesis and are upregulated in breast tumours that develop antioestrogen resistance. CONCLUSION: ERbeta has potential as a novel clinical prognostic marker in breast cancer, particularly in determining tumours that are resistant to tamoxifen.

Alternative Splicing↗
PubMed2000

Direct activation of oestrogen receptor-alpha by interleukin-6 in primary cultures of breast cancer epithelial cells.

Interleukin 6 (IL-6) is secreted by breast tumours and shows synergistic activity with 17beta-oestradiol (E2), leading to increases in reductive 17beta-hydroxysteroid dehydrogenase activity in breast cancer epithelial cells. However, the mechanisms involved are poorly understood. Using short-term epithelial cultures established from primary breast tumours, we have examined whether IL-6 could directly affect transcriptional activity of oestrogen reception alpha (ERalpha). Tumour epithelial cultures were established from 15 breast tumours, grown to 70% confluence and transiently transfected with a plasmid reporter containing the vitellogenin oestrogen response element and the luciferase coding sequence (ERE-TK-LUC). Following transfection, cells were incubated with E2, IL-6, the pure anti-oestrogen ZM 182780 or combinations of these substances for 48 h. Luciferase activity was then measured in cell lysates. E2 caused a dose-dependent increase in luciferase expression, causing a maximum threefold stimulation at 100 pM. In the presence of IL-6, transcriptional activity was increased by up to 2.5-fold in ERalpha+ cultures (11/15). In combination with E2, synergistic effects were observed with increases in luciferase activity of up to sixfold over controls. This effect could be blocked by treatment with ZM 182780. Pre-incubation of cells with an antibody directed against the signalling component of IL-6, gp130, was ineffective in blocking the E2 response. This antibody reduced, but did not completely block the effect of IL-6 either alone or in combination with E2, suggesting cross-talk between the two signalling pathways. In conclusion, these results provide evidence for direct transcriptional activation of ERalpha by IL-6.

Breast Neoplasms↗
PubMed2000

Identification of wild-type and exon 5 deletion variants of estrogen receptor beta in normal human mammary gland.

We have examined messenger RNA (mRNA) expression of estrogen receptor (ER) alpha, wild-type ERbeta (mRNA and protein), and ERbeta exon 5 deletion variants (ERbeta delta5) in samples of normal human mammary gland obtained from 37 premenopausal subjects undergoing reduction mammoplasty. Comparing individual expression, ERbetaP mRNA predominated, expressed in 34 of 37 samples (91%), whereas ERalpha was found in 21 of 37 cases (57%). Receptor combinations were then analyzed and compared. Most samples either coexpressed ERalpha with ERbeta (54%) or expressed just ERbeta (38%). Immunohistochemical analysis revealed that ERbeta mRNA expression mirrored that of protein. Immunoreactivity was observed in the nucleus with additional evidence of cytoplasmic staining in those epithelial cells lining the breast ducts. Sporadic immunoreactivity was also detected in stromal cells. Expression of wild type and ERbeta delta5 was analyzed, and their association with ERalpha was compared. Most samples coexpressed wild-type ERbeta and the splice variant (62%; P = 0.05), with 30% exclusively expressing wild-type ERbeta. Although samples coexpressing wild type and variant ERbeta showed no statistical association with ERalpha, those samples expressing only wild-type ERP, showed a trend toward associations with ERalpha (P = 0.07). In conclusion, our data would support a role for ERbeta in the normal human mammary gland, where we propose it may be the dominant receptor.

Adolescent↗
PubMed1999

Increased expression of estrogen receptor beta mRNA in tamoxifen-resistant breast cancer patients.

Tamoxifen is currently the first-line therapy for treatment of hormone-dependent breast cancer. However, despite initial benefits, most patients eventually relapse. Two groups of patients were identified: (a) a tamoxifen-sensitive group (n = 8); and (b) a tamoxifen-resistant group (n = 9). Using reverse transcription-PCR, the relative expression of mRNA for both estrogen receptor (ER) beta and transforming growth factor beta1 was determined in each patient group and quantified against a known reference standard. ER-beta mRNA was significantly up-regulated in the tamoxifen-resistant group as compared with the tamoxifen-sensitive group (P = 0.001 by Fisher's exact test), and, consistent with previous findings, transforming growth factor beta1 was also up-regulated in the tamoxifen-resistant cohort (P = 0.02). The importance of ER-beta in tamoxifen resistance was validated using tamoxifen-sensitive and -resistant cell lines, in which it was demonstrated that ER-beta mRNA was significantly up-regulated in the resistant cells. These results lend further support to a role for ER-beta as a poor prognostic factor in breast cancer.

Aged↗