scholarly journals Features of tumor heterogeneity in regional metastasis of breast cancer

2021 ◽  
Vol 102 (5) ◽  
pp. 716-725
Author(s):  
K K Konyshev ◽  
S V Sazonov
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Tumor Heterogeneity ◽  
Tumor Tissue ◽  
Clonal Evolution ◽  
Clinical Manifestations ◽  
Progesterone Receptors ◽  
Primary Tumors ◽  
Regional Metastases

The review looked at the issues of tumor heterogeneity in breast cancer. Tumor heterogeneity is classified according to the main feature demonstrating regional differences within a tumor (for example, heterogeneity of clinical manifestations, histological heterogeneity, heterogeneity of protein expression, etc.) and by tumor regions (differences between primary tumors and metastases, differences between cell clones within a single tumor node, etc.). Temporal heterogeneity is also distinguished, which manifests itself in the clonal evolution of tumor cells. The review covers the heterogeneity in the expression of four biomarkers from the gold standard for immunohistochemical staining of breast cancer: estrogen receptors, progesterone receptors, Her2/neu and Ki67 in primary tumor tissue and regional metastases. According to various studies, discordance in estrogen receptor status of primary tumor cells and metastases was observed with a frequency of 4 to 62%, progesterone receptors from 12 to 54%, Her2/neu from 0 to 24%, Ki67 from 4 to 39%. The results of studies of changes in the expression levels of individual markers in breast cancer metastases, as well as the heterogeneity of surrogate subtypes of tumor tissue in metastasis, are briefly described. Possible reasons for heterogeneity in the expression of key prognostic and predictive markers by primary tumor and metastatic cells, such as artificial factors at the preanalytic and analytic stages of the study, polyclonality of the primary tumor before metastasis, clonal evolution of tumor cells during metastasis, selection of tumor clones under the therapy are highlighted.

Distribution of Estrogen and Progesterone Receptors in Primary Tumor and Lymph Nodes in Individual Patients with Breast Cancer

1984 ◽  
Vol 70 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Danila Coradini ◽  
Vera Cappelletti ◽  
Patrizia Miodini ◽  
Enrico Ronchi ◽  
Gianfranco Scavone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Progesterone Receptors ◽  
Cancer Tissue ◽  
Primary Tumors ◽  
Er Positive ◽  
Malignant Lymph Nodes ◽  
Negative Lymph Nodes ◽  
Primary Breast Cancer Tissue

Primary breast cancer tissue and lymph nodes were obtained from 48 patients. Estrogen receptors (ER) and progesterone receptors (PgR) were determined by a dextran-coated charcoal assay. ER were present in 72.9 % of the primary tumors and in 62.4 % of the malignant lymph nodes, whereas PgR were present in 73.0 % and 50.0 % of the cases, respectively. The primary tumor and the corresponding malignant lymph nodes showed an identical ER and PgR status, i.e., both tumor sites were receptor positive or both receptor negative in 89.6 % and 77.1 %, respectively. However, 10.4 % of the patients had ER-positive tumors but ER-negative lymph nodes and 22.9 % had PgR-positive primaries with PgR-negative lymph nodes. No receptor-positive lymph nodes showed a combination with receptor-negative primary tumor. This preliminary data shows that receptor-positive malignant lymph nodes mostly display the same receptor status as the corresponding primary tumor, whereas receptor-negative lymph nodes may have a receptor-positive primary tumor.

Estrogen receptor (ER) status of disseminated tumor cells in the bone marrow of breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21013-21013
Author(s):  
F. N. Tanja ◽  
N. Krawczyk ◽  
D. Wallwiener ◽  
S. Becker ◽  
E. Solomayer
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Hormone Receptor ◽  
Primary Breast Cancer ◽  
Disseminated Tumor Cells ◽  
Breast Cancer Patients ◽  
Primary Tumors

21013 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis. These patients may benefit from adjuvant endocrine therapy since cytotoxic agents are not able to completely eliminate DTCs as previously shown. Only patients with hormone receptor positive breast cancer are eligible for hormonal treatment. The ERa status is routinely defined in primary tumor tissue. However, the ERa status of DTC may differ compared to the primary tumor. Therefore, the aims of this study were (1) to determine the ERa status of DTC in BM of breast cancer patients, (2) and to compare the ERa status of DTC and corresponding primary tumors. Methods: BM aspirates from 251 primary breast cancer patients were included into the study. A double immunofluorescence staining procedure was established for the identification of cytokeratin-positive (CK)/ERa positive cells. ERa status of the primary tumor was immunohistochemically assessed using the same antibody against ERa. Results: In 105 of 251 (42%) breast cancer patients CK-positive cells could be detected in BM. The number of detected cells ranged between 1 and 13 / cells per 2*106 mononuclear cells. Disseminated tumor cells demonstrated ERa positivity in 13 (12%) of these 105 patients. The ERa expression on DTC was heterogeneous in 10 of 13 (79%) patients. Concordance rate of ERa status between primary tumor and DTC was 27%. Only 11 of 83 patients with ER a positive tumors had also ERa positives DTC. Conclusions: (1)The hormone receptor status between primary tumor and corresponding DTC is disconcordant. (2)This discrepancy may explain the rate of non-responders to adjuvant endocrine therapy despite ER-positive primary tumors. (3)These patients may benefit from adjuvant therapy regimens based on antibody strategies or bisphosphonates. No significant financial relationships to disclose.

scholarly journals Whole Genome Sequencing in single CTC improves clinical outcome in Her-2 negative breast cancer patients

2020 ◽  
Author(s):  
Bo Yu ◽  
Yongping Li ◽  
Hao Yuan ◽  
Bin Zhang ◽  
Xiaofei Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Genome Sequencing ◽  
Primary Tumor ◽  
Tumor Tissue ◽  
Whole Genome ◽  
Breast Cancer Patients ◽  
Her2 Gene ◽  
Her 2

Abstract Background Tumor tissues are usually highly heterogeneous and difficult to characterize which could mislead treatment strategy. Circulating tumor cells (CTCs) represent the most active and invasive tumor cells. This study explored the feasibility of individualized treatment of breast cancer patients based on genome sequencing of single cell CTC. Methods Twenty-four CTCs were identified in three patients with breast cancer. For each patient, one polyploid CTC was captured and on which the whole genome sequencing (WGS) was performed. Based on the histopathological Her-2 status in tumor tissue and the HER2 gene status in WGS results of CTC, we adjusted treatment strategies, and monitored disease progression. Results Patient ID1 and ID2 are Her-2 positive in both primary tumor and HER2 abnormal in the DNA of CTC. In patient ID3, histological examination of primary tumor and liver metastases revealed Her-2 negative, but the WGS analysis of CTC showed that the HER2 gene was amplified and mutated. After adjusting treatment according to the results of CTC sequencing, the liver metastases and pleural effusion were significantly reduced, CTC number and ctDNA burden were decreased. In addition, some potential therapeutic targets and mutations in drug-resistant genes were found. Conclusion The results of CTC sequencing effectively guided treatment of a patient with HER2 gene amplification/mutation in CTC but with Her-2 negative on tumor tissue. CTC sequencing is useful in resolving the heterogeneity of tumors and providing precision medicine for patients.

scholarly journals Cancer gene panel analysis of cultured circulating tumor cells and primary tumor tissue from patients with breast cancer

2017 ◽  
Vol 13 (6) ◽  
pp. 4627-4632 ◽  
Author(s):  
Eunjoo Hwang ◽  
Ji-Hyun Uh ◽  
Hye Seon Lee ◽  
Cham Han Lee ◽  
Soo Jeong Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Primary Tumor ◽  
Tumor Tissue ◽  
Gene Panel ◽  
Panel Analysis ◽  
Cancer Gene

scholarly journals MHC Class 1 and PDL-1 Status of Primary Tumor and Lymph Node Metastatic Tumor Tissue in Gastric Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Ibrahim Halil Erdogdu
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Tumor Tissue ◽  
Metastatic Tumor ◽  
Tumor Escape ◽  
Metastatic Tumors ◽  
Primary Tumors

The prognosis of metastatic gastric cancer is poor. Despite the use of VEGF-, EGFR-, and HER2-targeting agents, prognosis is still poor in advanced gastric cancer. Although cancer immunotherapy responds well in some patients, clinical use is limited due to unanswered patients. For this reason, it is necessary to know the characteristics of primary and metastatic cancer cells for patient selection for immunotherapy and additional criteria are required. MHC-1 downregulation is most frequently observed in the tumor escape mechanism of cancer cells from the immune system. MHC-1 downregulation with increased PDL-1 expression of cancer cells has an important role in immune escape. MHC-1 downregulation and PDL-1 expression have been shown in many types of cancers. However, there is no study on the status of MHC-1 and PDL-1 in primary and metastatic tumor tissue. In this study, MHC-1 and PDL-1 score in primary and metastatic tumor cells was evaluated in 43 gastric cancer patients with lymph node metastasis. According to our results, the primary tumor PDL-1 score was correlated with the number of metastatic lymph nodes (r=0.258; p=0.024) and primary tumor size (r=0.341; p=0.045). A similar correlation was found between the primary tumor PDL-1 score and the metastatic tumor PDL-1 score (r=0.213; p=0.015). In our study, MHC-1 was found to be higher in primary tumors than metastatic tumors, although not statistically significant (p=0.054). The results of our study showed high MHC-1 and low PDL-1 expression in primary tumors and low MHC-1 and high PDL-1 expression in metastatic tumors. These results reveal different biological characteristics of primary and metastatic tumor cells.

scholarly journals Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1213
Author(s):  
Zihe Huo ◽  
Mariana Sá Santos ◽  
Astrid Drenckhan ◽  
Stefan Holland-Cunz ◽  
Jakob R. Izbicki ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Tumor Cells ◽  
Cell Lines ◽  
Adhesion Strength ◽  
Primary Tumor ◽  
Carcinoma Cell ◽  
Metastatic Potential ◽  
Primary Tumors ◽  
Metastatic Cell ◽  
Carcinoma Cell Lines

Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential.

scholarly journals Differential expression of cyclin A2 in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Differential Expression ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Differentially Expressed ◽  
Primary Tumors ◽  
Ductal Cells ◽  
Cyclin A2

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding cyclin A2, CCNA2, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). CCNA2 was also differentially expressed in bulk tumor in human breast cancer (3). CCNA2 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of CCNA2 in primary tumors of the breast was correlated with overall survival in patients with basal-like type cancer, while within triple negative breast cancer, primary tumor expression of CCNA2 was correlated with overall survival in patients with basal-like 1, basal-like 2, and mesenchymal subtype disease. CCNA2 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.

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

1987 ◽  
Vol 5 (11) ◽  
pp. 1779-1782 ◽  
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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