Different Proliferation Patterns in Breast Cancer: AgNOR Measurements in ER-Negative and ER-Positive Tumor Cells

The relation between estrogen receptors (ER) and argyrophilic nucleolar organizer regions (AgNORs)in situwithin human breast cancer cells was analyzed. For AgNOR measurements in 49 invasive breast carcinomas, a new reproducible staining method for dual demonstration of ER and AgNORs was applied. Quantitative AgNOR variables were determined in ER‐positive and ER‐negative tumor cells by digital image analysis. The relationships between AgNOR parameters of ER‐positive and ER‐negative cells and other prognostic factors of breast cancer [Bloom–Richardson‐Grading and growth fraction (Ki‐67 index)] were investigated. A higher AgNOR content in ER‐negative cells and a special clustering phenomenon in ER‐positive tumor cells were found. Correlation with other criteria of malignant potential could be exclusively demonstrated for ER‐negative cells. ER‐negative cells of breast cancer can be characterized as the more malignant and possibly prognosis‐dictating cell fraction. Thus, ER‐negative cells probably contribute more to the progression of the tumor disease and furthermore to the prognosis than ER‐positive cells. We recommend measurement AgNORs exclusively in ER‐negative cells of breast cancer.

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Antitumor Activity and Underlying Mechanism of Phomoxanthone B in MCF7 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620999201124215511 ◽

2020 ◽

Vol 20 ◽

Author(s):

Chuan Chen ◽

Ziyue Zhao ◽

Qian Dong ◽

XueHui Gao ◽

Huibin Xu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Antitumor Activity ◽

Oxidative Phosphorylation ◽

Tumor Cells ◽

Transcriptome Analysis ◽

Mcf7 Cells ◽

Er Positive ◽

Induced Apoptosis ◽

Positive Breast Cancer

Background:: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B（PXB）and Phomoxanthone A（PXA）are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. Objective:: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. Methods:: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. Results:: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. Conclusion:: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

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Sequential silver staining and in situ hybridization reveal a direct association between rDNA levels and the expression of homologous nucleolar organizing regions: a hypothesis for NOR structure and function

Journal of Cell Science ◽

10.1242/jcs.111.10.1433 ◽

1998 ◽

Vol 111 (10) ◽

pp. 1433-1439

Author(s):

F. Zurita ◽

R. Jimenez ◽

M. Burgos ◽

R.D. de la Guardia

Keyword(s):

Transcription Factors ◽

In Situ Hybridization ◽

Silver Staining ◽

Organizer Region ◽

Nucleolar Organizer ◽

Interindividual Variation ◽

Nucleolar Organizer Regions ◽

Single Pair ◽

Ribosomal Cistrons

We have developed a procedure for sequential silver staining and in situ hybridization to analyze the relationship between the amount of rDNA present in nucleolar organizer regions, as estimated by in situ hybridization, and their level of expression, as estimated by the silver signal. For simplicity we used cells from the insectivorous mole Talpa occidentalis, which have a single pair of nucleolar organizer regions in chromosome pair 3. The relative content of ribosomal cistrons was also related to the hierarchy of activation of the nucleolar organizer regions present in this chromosomal pair. Statistical analyses demonstrated that both the relative level of expression and the activation hierarchy depended mainly on the number of ribosomal cistrons in nucleolar organizer regions. We propose a functional two-step hypothesis, which is consistent with most known data concerning interchromosomal, intercellular and interindividual variation in a number of plant and animal species, including Talpa occidentalis. In step one, the first available transcription factors bind randomly to the ribosomal promoters, such that larger nucleolar organizer regions are more likely to recruit them. In the second step the remaining transcription factors are recruited in a cooperative way, thus completing activation of one nucleolar organizer region, before the next one becomes active.

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Analysis of Low Estrogen Receptor (ER+) Breast Carcinomas in a Large Community Breast Cancer Center in Northern California

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqab191.051 ◽

2021 ◽

Vol 156 (Supplement_1) ◽

pp. S26-S27

Author(s):

G Bulusu ◽

K Duncan ◽

A Wheeler

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Histological Grade ◽

Statistical Significance ◽

Cancer Center ◽

Pathology Report ◽

Breast Cancers ◽

Breast Carcinomas ◽

Ki 67 ◽

Er Positive

Abstract Introduction/Objective Estrogen Receptor (ER) expression in breast cancers is a crucial factor for endocrine therapy in patients with tumors expressing ER in ≥1% of tumor cells. The 2019 guidelines published by ASCO/CAP states that breast cancers that have a 1% to 10% of cells staining Estrogen Receptor (ER) positive should be reported as ER Low Positive cases. This study aims to address this subset of low-positive ER tumors and compare the clinical features to other known breast cancer subtypes. Methods/Case Report We conducted a retrospective review of a prospectively maintained breast cancer registry from 2013 to 2021 at Mills-Peninsula Medical Center, a Sutter Health Affiliate. The study reviewed patient charts with respect to the pathology report, operative report, chemotherapy regimen, and clinical outcomes. Statistical analyses were conducted using R Project for Statistical Coding, with The Student’s T-test used to compare continuous variables. Two-sided P values less than 0.05 indicate statistical significance. Results (if a Case Study enter NA) Our study identified 1316 cases of invasive breast carcinomas, of which 29 (2.16%) demonstrated ER Low-Positive expression. We aimed to evaluate the clinical and pathological features, such as histological grade, ER, PR, HER-2, Ki-67%, and patient age for these tumors. We found that ER Low-Positive tumors demonstrated higher mean histological grade morphology (2.5 out of 3, p<0.001) that was similar to that of Triple Negative Breast Cancers (TNBC) (3 of 3, p<0.001) than to High ER-Positive (1.6 of 3, p<0.001) cancers. Further observations, through examining proliferation rates by utilizing the Ki-67 index, indicate comparative trends between the ER Low-Positive cohort and the TNBC cohort. Conclusion The results suggest that the ER Low-Positive carcinomas, despite reported as ER-positive cases, present with similar clinicopathological features to those of ER-negative tumors. Through this study and future research, we would like to emphasize a stricter set of guidelines that can be adopted to reduce variability for reporting biomarkers. This standardization will allow oncologists to provide more appropriate treatment options and improve the quality of patient care.

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Detection of estrogen receptor in bone marrow from patients with metastatic breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.11.1779 ◽

1987 ◽

Vol 5 (11) ◽

pp. 1779-1782 ◽

Cited By ~ 10

Author(s):

U Berger ◽

J L Mansi ◽

P Wilson ◽

R C Coombes

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Endocrine Therapy ◽

Tumor Cells ◽

Epithelial Membrane Antigen ◽

Metastatic Breast ◽

Breast Cancers ◽

Double Staining ◽

Primary Tumors ◽

Er Positive

We devised a method of detecting estrogen receptors (ER) in bone marrow metastases from patients with breast cancer. The method involves a sequential double-staining immunocytochemical technique, with a monoclonal antibody to ER and a polyclonal antibody recognizing epithelial membrane antigen to confirm the epithelial nature of suspected tumor cells. Twenty-seven patients were assessed: ten were found to have ER-positive tumor cells in the bone marrow; ten had ER-negative cells; and the remaining seven patients had no tumor cells in the bone marrow smears. Of the ten patients with ER-positive cells, eight (80%) either had a response to endocrine therapy, implying that they possess ER-positive breast cancers, or had ER-positive primary tumors as determined by the dextran-coated charcoal biochemical assay (DCC). Of the ten patients with ER-negative cells in the bone marrow, eight failed to respond to endocrine therapy. This technique therefore provides a means of predicting which patients will respond to endocrine therapy, and is particularly important in those patients whose ER status is unknown.

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Influence of endocrine therapy on the ratio of androgen receptor (AR) to estrogen receptor (ER) positive circulating epithelial tumor cells (CETCs) in breast cancer

Journal of Translational Medicine ◽

10.1186/s12967-018-1724-z ◽

2018 ◽

Vol 16 (1) ◽

Cited By ~ 3

Author(s):

Monika Pizon ◽

Daniel Lux ◽

Ulrich Pachmann ◽

Katharina Pachmann ◽

Dorothea Schott

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Androgen Receptor ◽

Endocrine Therapy ◽

Tumor Cells ◽

Epithelial Tumor ◽

Er Positive ◽

Epithelial Tumor Cells

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Recurrent anaplastic ganglioglioma: pathological characterization of tumor cells

Journal of Neurosurgery ◽

10.3171/jns.1996.84.6.1055 ◽

1996 ◽

Vol 84 (6) ◽

pp. 1055-1059 ◽

Cited By ~ 38

Author(s):

Atushi Sasaki ◽

Junko Hirato ◽

Yoichi Nakazato ◽

Masaru Tamura ◽

Hirotaka Kadowaki

Keyword(s):

Tumor Cells ◽

Glial Cells ◽

Organizer Region ◽

Nucleolar Organizer Region ◽

Nucleolar Organizer ◽

Left Frontal Lobe ◽

Ki 67 ◽

Content Type ◽

Initial Tumor ◽

Mib 1

✓ A total resection of a left frontal lobe tumor in a 26-year-old man revealed differentiated ganglioglioma with small foci of atypical glial cells exhibiting mild atypia. Six and one-half years later, a large, well-demarcated tumor recurred; at that time, histological analysis revealed both typical ganglioglioma and highly cellular anaplastic areas, the latter predominating. Although the patient subsequently underwent total and subtotal resections, radiation therapy, and chemotherapy, tumors continued to recur at progressively shorter intervals and he died at the age of 35 years. Biopsies of tissue obtained at the last three resections and the autopsy revealed only anaplastic tumor cells. Routine histological examinations indicated that these tumors were uniformly composed of undifferentiated cells. However, pathological studies using immunohistochemical analysis, electron microscopy, and immunoblot analysis demonstrated that a small number of recurrent anaplastic cells had astrocytic features. Results of Ki-67/MIB-1 labeling and silver nucleolar organizer region counts for those cells were high for glial tumors. A retrospective study of the initial tumor showed slightly high MIB-1 labeling for atypical glial cells. This case is characterized by pathological findings of recurrent tumors that correspond to an unusual form of malignant glioma exhibiting slight astrocytic differentiation. The present case suggests that a longer follow-up period (> 5 years) is necessary in cases of ganglioglioma with mild atypia and that careful examinations, including proliferating potential analysis of initial tumor cells, could be important for the diagnosis and treatment of ganglioglioma.

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