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” ERa and the more recently described ERb. Although much is known about ERa at the mRNA and protein levels, our knowledge of the expression and distribution of ERb protein is much more limited. The aim of this study was to compare the cellular distribution of ERa and ERb 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 ERa, ERb, and the progesterone receptor. The staining pattern for each antibody was evaluated and compared. RESULTS: ERa was restricted to the cell nuclei of epithelial cells lining ducts and lobules. Although ERb 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 ERb suggests that it may be the dominant ER in the mammary gland where it may be acting as a natural suppressor

INTER-annual/decadal variability of the north Aegean Sea hydrodynamics over 1960-2000

Results from a high-resolution hindcast model experiment, supported by available observations, reveal an increasing salinity trend in the north Aegean during the Eastern Mediterranean Transient (EMT), largely controlled by increases in the flow rate and salinity of water masses of Levantine origin entering the domain through the Myconos-Ikaria strait as a response to an acceleration of the Aegean thermohaline cell. Changes in the Dardanelles inflow (increasing salinity) and in the surface freshwater flux (increasing Evaporation-Precipitation), although both contribute to a higher salt content of the basin during the EMT, play a minor role in the inter-annual/decadal variability of the freshwater budget. A long-term decreasing temperature trend is observed from the 1960s to the early 1990s. It is superimposed on the salinity-preconditioning phase over the 1980s and early 1990s. Both signals are, concomitantly, favouring conditions for intense Dense Water Formation (DWF) in the north Aegean Sea. In addition, the northward displacement of the Black Sea Water front over the EMT, leads to the expansion of convective cells towards the north and to higher formation rates associated with both colder and saltier surface waters

Changing water cycle and freshwater transports in the Atlantic Ocean in observations and CMIP5 models

Observations over the last 40 years show that the Atlantic Ocean salinity pattern has amplified, likely in response to changes in the atmospheric branch of the global water cycle. Observational estimates of oceanic meridional freshwater transport (FWT) at 26.5° N indicate a large increase over the last few decades, during an apparent decrease in the Atlantic Meridional Overturning Circulation (AMOC). However, there is limited observation based information at other latitudes. The relative importance of changing FWT divergence in these trends remains uncertain. Ten models from the Coupled Model Intercomparison Project Phase 5 are analysed for AMOC, FWT, water cycle, and salinity changes over 1950–2100. Over this timescale, strong trends in the water cycle and oceanic freshwater transports emerge, a part of anthropogenic climate change. Results show that as the water cycle amplifies with warming, FWT strengthens (more southward freshwater transport) throughout the Atlantic sector over the 21st century. FWT strengthens in the North Atlantic subtropical region in spite of declining AMOC, as the long-term trend is dominated by salinity change. The AMOC decline also induces a southward shift of the Inter-Tropical Convergence Zone and a dipole pattern of precipitation change over the tropical region. The consequent decrease in freshwater input north of the equator together with increasing net evaporation lead to strong salinification of the North Atlantic sub-tropical region, enhancing net northward salt transport. This opposes the influence of further AMOC weakening and results in intensifying southward freshwater transports across the entire Atlantic

Oestrogen receptor beta: how should we measure this?

British Journal of Cancer (2002) 87, 687–687. doi:10.1038/sj.bjc.6600534 www.bjcancer.co

Immunohistochemical detection of ERβ in breast cancer: towards more detailed receptor profiling?

Oestrogen receptor (ER) is used routinely to predict endocrine responsiveness in patients with breast cancer. A second ER, ERβ has been described but its significance remains undefined; most studies have described mRNA levels rather than protein expression. Here, we demonstrate for the first time, immunohistochemical detection of ERβ in archival breast tumours. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Mediterranean Sea response to climate change in an ensemble of twenty first century scenarios

The Mediterranean climate is expected to become warmer and drier during the twenty-first century. Mediterranean Sea response to climate change could be modulated by the choice of the socio-economic scenario as well as the choice of the boundary conditions mainly the Atlantic hydrography, the river runoff and the atmospheric fluxes. To assess and quantify the sensitivity of the Mediterranean Sea to the twenty-first century climate change, a set of numerical experiments was carried out with the regional ocean model NEMOMED8 set up for the Mediterranean Sea. The model is forced by air–sea fluxes derived from the regional climate model ARPEGE-Climate at a 50-km horizontal resolution. Historical simulations representing the climate of the period 1961–2000 were run to obtain a reference state. From this baseline, various sensitivity experiments were performed for the period 2001–2099, following different socio-economic scenarios based on the Special Report on Emissions Scenarios. For the A2 scenario, the main three boundary forcings (river runoff, near-Atlantic water hydrography and air–sea fluxes) were changed one by one to better identify the role of each forcing in the way the ocean responds to climate change. In two additional simulations (A1B, B1), the scenario is changed, allowing to quantify the socio-economic uncertainty. Our 6-member scenario simulations display a warming and saltening of the Mediterranean. For the 2070–2099 period compared to 1961–1990, the sea surface temperature anomalies range from +1.73 to +2.97 °C and the SSS anomalies spread from +0.48 to +0.89. In most of the cases, we found that the future Mediterranean thermohaline circulation (MTHC) tends to reach a situation similar to the eastern Mediterranean Transient. However, this response is varying depending on the chosen boundary conditions and socio-economic scenarios. Our numerical experiments suggest that the choice of the near-Atlantic surface water evolution, which is very uncertain in General Circulation Models, has the largest impact on the evolution of the Mediterranean water masses, followed by the choice of the socio-economic scenario. The choice of river runoff and atmospheric forcing both have a smaller impact. The state of the MTHC during the historical period is found to have a large influence on the transfer of surface anomalies toward depth. Besides, subsurface currents are substantially modified in the Ionian Sea and the Balearic region. Finally, the response of thermosteric sea level ranges from +34 to +49 cm (2070–2099 vs. 1961–1990), mainly depending on the Atlantic forcing

A divergent role for estrogen receptor-beta in node-positive and node-negative breast cancer classified according to molecular subtypes: an observational prospective study

Introduction: Estrogen receptor-alpha (ER-alpha) and progesterone receptor (PgR) are consolidated predictors of response to hormonal therapy (HT). In contrast, little information regarding the role of estrogen receptor-beta (ER-beta) in various breast cancer risk groups treated with different therapeutic regimens is available. In particular, there are no data concerning ER-beta distribution within the novel molecular breast cancer subtypes luminal A (LA) and luminal B (LB), HER2 (HS), and triple-negative (TN). Methods: We conducted an observational prospective study using immunohistochemistry to evaluate ER-beta expression in 936 breast carcinomas. Associations with conventional biopathological factors and with molecular subtypes were analyzed by multiple correspondence analysis (MCA), while univariate and multivariate Cox regression analysis and classification and regression tree analysis were applied to determine the impact of ER-beta on disease-free survival in the 728 patients with complete follow-up data. Results: ER-beta evenly distributes (55.5%) across the four molecular breast cancer subtypes, confirming the lack of correlation between ER-beta and classical prognosticators. However, the relationships among the biopathological factors, analyzed by MCA, showed that ER-beta positivity is located in the quadrant containing more aggressive phenotypes such as HER2 and TN or ER-alpha/PgR/Bcl2- tumors. Kaplan-Meier curves and Cox regression analysis identified ER-beta as a significant discriminating factor for disease-free survival both in the node-negative LA (P = 0.02) subgroup, where it is predictive of response to HT, and in the node-positive LB (P = 0.04) group, where, in association with PgR negativity, it conveys a higher risk of relapse. Conclusion: Our data indicated that, in contrast to node-negative patients, in node-positive breast cancer patients, ER-beta positivity appears to be a biomarker related to a more aggressive clinical course. In this context, further investigations are necessary to better assess the role of the different ER-beta isoforms

Oestrogen receptor β and neoadjuvant therapy with tamoxifen: prediction of response and effects of treatment

In order to elucidate the relative importance of oestrogen receptor (ER)α, ERβ and an ERβ variant (ERβ2/βcx) in the response of breast cancers to tamoxifen, tumour levels of each receptor were assessed in 36 patients before and after 3 months of neoadjuvant treatment with tamoxifen (20 mg daily). All patients were postmenopausal women presenting with large ERα-positive breast cancers. Clinical response to treatment was assessed by tumour volume changes as determined from sequential ultrasounds and pathological response by comparison of the tumour morphology before and after treatment. Of 33 cases, 23 (70%) were classified as having a clinical response and 16 (48%) as having a response pathologically. All tumours stained positively for ERα and ERβ and 15 out of 33 (45%) for ERβ2/βcx. There were no significant differences in quantitative expression of any receptor between tumours that subsequently responded and that did not, whether response was assessed clinically or pathologically. Tamoxifen treatment was associated with a decrease in ERα, but an increase was the most frequent change (17 out of 33) in ERβ, and no consistent change was evident in staining of the ERβ2/βcx variant. In summary, ERβ1 and ERβ2/βcx variant protein are detected in ERα-positive breast tumours but their expression is not associated with a response to tamoxifen. Differential changes in ERα and ERβ were seen with treatment