Cytoplasmic colocalization of RXRα and PPARγ as an independent negative prognosticator for breast cancer patients

Retinoid X receptor α (RXRα) is a nuclear receptor (NR) which functions as the primary heterodimeric partner of other NRs including the peroxisome proliferator-activated receptor γ (PPARγ). We previously reported that, in breast cancers (BC), the subcellular localization of these two receptors was strongly associated with patient prognosis. In the present work, we investigated the prognosis value of the combined cytoplasmic expression of RXRα and PPARγ using a retrospective cohort of 250 BC samples. Patients with tumors expressing both NRs in tumor cell cytoplasm exhibited a significant shorter overall (OS) and disease-free survival (DFS). This was also observed for patients with stage 1 tumors. Cox univariate analysis indicated that patients with tumors coexpressing RXRα and PPARγ in the cytoplasm of tumor cells have a decreased 5 y OS rate. Cytoplasmic co-expression of the two NRs significantly correlated with HER2 positivity and with NCAD and CD133, two markers of tumor aggressiveness. Finally, in Cox multivariate analysis, the co-expression of RXRα and PPARγ in the cytoplasm appeared as an independent OS prognosticator. Altogether, this study demonstrates that the cytoplasmic co-expression of RXRα and PPARγ could be of relevance for clinicians by identifying high-risk BC patients, especially amongst those with early and node-negative disease

Prognostic relevance of nuclear receptors in relation to peritumoral inflammation and tumor infiltration by lymphocytes in breast cancer

The prognostic impact of tumor-infiltrating lymphocytes (TILs) is intensively investigated in breast cancer (BC). It is already known that triple-negative breast cancer (TNBC), the most aggressive type of BC, has the highest percentage of TILs. In addition, there is an influence of steroid hormone receptor expression (type I nuclear receptors) on TIL subpopulations in breast cancer tissue. The link between type II nuclear receptors and the level of TILs is unclear. Therefore, the aim of this study was to quantify TILs in a panel of 264 sporadic breast cancers and investigate the correlation of TIL levels with type I and II nuclear receptors expression. TIL levels were significantly increased in the subgroup of TNBC. By contrast, they decreased in estrogen (ER)- or progesterone receptor (PR)-positive cases. Moreover, TIL levels were correlated with type II nuclear receptors, including PPARγ, with a significant inverse correlation of the nuclear form (r = −0.727, p 15% showed a significantly decreased overall survival. In addition, peritumoral inflammation was also quantified in BC tissue samples. In our cohort, although the level of peritumoral inflammation was not correlated with OS, it determined the prognostic value of ER, PR, and PPARγ in BC. Altogether, the present study provides a differentiated overview of the relations between nuclear receptor expression, TIL levels, peritumoral inflammation, and prognosis in BC

Th2/Th17 cell associated cytokines found in seroma fluids after breast cancer surgery

Purpose The development of a seroma after breast cancer surgery is a common postoperative complication seen after simple mastectomy and axillary surgery. We could recently demonstrate that breast cancer patients undergoing a simple mastectomy with subsequent seroma formation developed a T-helper cell increase within the aspirated fluid measured by flow cytometry. The same study revealed a Th2 and/or a Th17 immune response in peripheral blood and seroma fluid of the same patient. Based on these results and within the same study population, we now analyzed the Th2/Th17 cell associated cytokine content as well as the best known clinical important cytokine IL-6. Methods Multiplex cytokine measurements (IL-4, IL-5, IL-13, IL-10, IL-17, and IL-22) were done on 34 seroma fluids (Sf) after fine needle aspiration of patients who developed a seroma after a simple mastectomy. Serum of the same patient (Sp) and that of healthy volunteers (Sc) were used as controls. Results We found the Sf to be highly cytokine rich. Almost all analyzed cytokines were significantly higher in abundance in the Sf compared to Sp and Sc, especially IL-6, which promotes Th17 differentiation as well as suppresses Th1 differentiation in favor of Th2 development. Conclusion Our Sf cytokine measurements reflect a local immune event. In contrast, former study results on T-helper cell populations in both Sf and Sp tend to demonstrate a systemic immune process

323P Macrophage population analysis of the breast cancer microenvironment within the context of seroma formation after mastectomy (SerMa pilot study) [Abstract]

Background The primary goal of the SerMa pilot study was to identify possible immunological/inflammatory factors related to seroma formation after mastectomy and first diagnosis of breast cancer. CD68 is a common marker for tumor-associated monocytes and macrophages in general. CD163 is used to detect M2-polarized macrophages. Both are known to have an influence on defense reactions and wound healing due to their immunomodulatory effect. Thus, the aim of this evaluation was to evaluate whether a correlation can be shown within the context of postoperative seroma formation. Methods From 100 patients meeting the criteria of the study, tumor tissue of 80 patients was available for evaluation. Immunohistochemical antibody staining against CD68 and CD163 was performed, and two groups were compared: Patients with and without seroma formation. The number of macrophages in the tumor microenvironment was manually quantified at three sites representative of each specimen in the entire field of view at a magnification of 40x lens. The mean value of the three areas was used for further analysis. Results For CD68, the range of the mean value was from 0 to 354 macrophages. The number of CD68-positive macrophages was significantly increased (p=0.036) in patients with seroma development (mean=45.31) compared to those without (mean=34.31). For CD163, the range extends from 0 to 309 macrophages. Again, the number of CD163-positive macrophages was significantly increased (p=0.027) in patients with postoperative seroma formation (mean=45.57) compared to patients without (mean=33.99). Conclusions These data demonstrate a significant correlation of CD68 and CD163 positive macrophages in the tumor microenvironment and seroma formation in the breast after mastectomy. This study was the first to investigate these possible relationships. As highly associated with immunological processes, the significant higher detection of CD68 and CD163 within the population of “Seroma developers” supports our study group’s previously published results on the identification of immunological markers in seroma fluid and thus the hypothesized relationship of seroma formation based on immunological/inflammatory processes

Einfluss von Tumor infiltrierenden Lymphozyten und Steroidrezeptoren sowie Genexpression-steuernder Proteine und epigenetischer Veränderungen auf das Überleben bei Patientinnen mit Zervixkarzinom [Abstract]

Der Grad der Infiltration durch TIL bei Zervixkarzinomen entscheidet über den Effekt des PRA_s und PRA_nuc, des GR_nuc_IRS und von LCOR. Bei einer schwachen Infiltration durch TIL ist der Progesteronrezeptor negativ, LCOR und der GC_nuc_IRS positiv mit dem Überleben korreliert. Bei moderater Infiltration ist PRA_s positiv mit dem Überleben korreliert. Bei starker Infiltration ist LCOR negativ mit dem Überleben korreliert, während für PRA_s nur ein positiver Trend besteht

Expression von Progesteron Rezeptor A im Stroma von Zervixkarzinomen: Korrelation mit dem Überleben [Abstract]

Patientinnen mit Adenokarzinom der Zervix uteri haben ein signifikant schlechteres Überleben als Patientinnen mit Plattenepithelkarzinomen. Neben schon bekannten Faktoren wie p53, NBP2_n ist auch die Expression von PRA sowohl im Stroma als auch im Kern mit einem signifikant schlechteren Überleben korreliert

Ärztliches "Sich Zeit nehmen" befürwortet – erste Ergebnisse der WAVES-Studie im Rahmen der Diagnosemitteilung Brustkrebs [Abstract]

Erste Ergebnisse der WAVES-Studie bestätigen die Annahme einer deutlich höheren Zufriedenheit von Patient:innen im Zusammenhang mit der Mitteilung der Erstdiagnose Brustkrebs, wenn sich die Ärztin / der Arzt Zeit dafür nahm, im Idealfall mindestens 30 Minuten. Der Bedarf an verbesserter Kommunikation hinsichtlich eines angemessenen Zeitrahmens für die Diagnoseübermittlung bei Brustkrebs-Erkrankten wird damit klar aufgezeigt. Diese Daten bieten die Grundlage für eine mögliche Umstrukturierung in der Behandlung Brustkrebs-Erkrankter, die bisher in der aktuellen Vergütungsstruktur nicht abgebildet ist. Die Studie rekrutiert weiterhin