scholarly journals Disseminated Tumor Cells in Bone Marrow of Gastric Cancer Patients: Correlation with Tumor Hypoxia and Clinical Relevance

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Larissa Bubnovskaya ◽  
Antonina Kovelskaya ◽  
Lilya Gumenyuk ◽  
Irina Ganusevich ◽  
Lesya Mamontova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
Overall Survival ◽  
Tumor Cells ◽  
Clinical Relevance ◽  
Tumor Hypoxia ◽  
Disseminated Tumor Cells ◽  
Vegf Expression ◽  
Primary Tumors ◽  
Gastric Cancer Patients

Aim.The evaluation of the clinical relevance of disseminated tumor cells (DTCs) in bone marrow (BM) of patients with gastric cancer (GC) and their association with primary tumor hypoxia.Patients and Methods.89 resected specimens were used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography.Results.DTCs were detected in 51.4% of GC patients with M0. There was significant correlation between frequency of DTCs in BM and level of tumor hypoxia (P<0.024). DTCs presence was accompanied with Flt-1 positivity of BM. The correlation between DTCs and tumor VEGF expression in patients with M0was shown (P<0.0248). Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients with M0(P<0.05). Overall survival (OS) of patients with M0and DTCs was shorter than that of patients without DTCs (patients in both groups were operated only) (P=0.0497).Conclusion.Appearance of DTCs correlates with hypoxia level in primary tumors. Detection of DTCs in GC patients may be relevant indicator for adjuvant chemotherapy using.

scholarly journals CXCR4 Expression in Gastric Cancer and Bone Marrow: Association with Hypoxia-Regulated Indices, Disseminated Tumor Cells, and Patients Survival

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Dmitry Osinsky ◽  
Antonina Kovelskaya ◽  
Larissa Bubnovskaya ◽  
Irina Ganusevich ◽  
Lilya Gumenyuk ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
Overall Survival ◽  
Tumor Cells ◽  
Clinical Characteristics ◽  
Tumor Hypoxia ◽  
Disseminated Tumor Cells ◽  
Cxcr4 Expression ◽  
Unfavourable Outcome ◽  
Vegf Expression

Aim. The analysis of the association of CXCR4 expression in gastric cancer (GC) and bone marrow (BM) with clinical characteristics. Patients and Methods. 65 patients with GC were investigated. Immunohistochemistry, immunocytochemistry, NMR-spectroscopy, and zymography were used. Results. CXCR4 was expressed in 78.5% of GC specimens and correlated with tumor hypoxia (P<0.05), VEGF expression (P<0.01), and gelatinases activity (P<0.05). CXCR4-positive cells in GC were detected in 80% of patients with disseminated tumor cells (DTCs). Overall survival (OS) of patients with CXCR4-positive tumors was poorer than that of patients with CXCR4-negative tumors (P=0.037). The CXCR4-positive cells in BM were found in 46% of all patients and in 56% of patients with DTCs. CXCR4 expression in BM was not associated with OS. Risk of unfavourable outcome is increased in patients with CXCR4-positive tumors (P<0.05). CXCR4 expression in BM was positively associated with DTCs, especially in patients with M0 category. Risk of unfavourable outcome is increased in patients with M0 category and with both CXCR4-positive BM and DTCs (P=0.03). Conclusions. CXCR4 expression in tumor was positively correlated with hypoxia level and VEGF expression in tumor as well as OS. CXCR4 expression in BM is associated with DTCs.

scholarly journals CD8 AND CD45RO T LYMPHOCYTES IN BONE MARROW OF GASTRIC CANCER PATIENTS: CORRELATION WITH DISSEMINATED TUMOR CELLS AND DISEASE OUTCOME

2015 ◽  
Vol 37 (1) ◽  
pp. 48-52
Author(s):  
S Osinsky ◽  
A Kovelskaya ◽  
L Bubnovskaya ◽  
D Osinsky ◽  
S Merentsev
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
T Cells ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Tumor Hypoxia ◽  
Disseminated Tumor Cells ◽  
Disease Outcome ◽  
Number Of Patients ◽  
Gastric Cancer Patients

Aim: To evaluate the association between the presence of CD8 and CD45RO T lymphocytes in bone marrow (BM), disseminated tumor cells (DTCs), tumor hypoxia and their impact on disease outcome. Material and methods: 91 naïve gastric cancer (GC) patients were enrolled into the study. DTCs, CD8- and CD45RO-positive T lymphocytes in BM were detected using immunocytochemistry. All patients were thoroughly informed about the study that was approved by the local ethics committee. Statistical analyses were done using NCSS2000/PASS2000 and Prism, version 4.03 software packages. Results: It was detected that 80.5 and 81.3% of patients had CD8- and CD45RO-positive T cells in BM, respectively. When DTCs were detected in BM, the number of patients with CD8-and CD45RO-positive T cells in BM were 86.1 and 84.4%, respectively. It was also determined that the number of patients with DTCs in BM with categories M0 and M1 and with CD8- and CD45RO-positive T cells in BM were 86.2 and 85.7%, 85.7 and 80.0%, respectively. The association between DTCs in BM and presence of CD8 and CD45RO T cells lymphocytes in BM was not found. At the same time it was shown the association between presence of CD8 and CD45RO T lymphocytes and survival. The presence of CD8- and CD45RO-positive T cells in BM were accompanied with significantly longer overall survival of patients compared to that of patients without CD8- and CD45RO-positive T cells in BM. Conclusion: Patients with the presence of CD8- and CD45RO-positive T cells in BM demonstrated better survival of GC patients than those with the absence of these cells in BM. It may be suggested that tumor cells in BM are controlled in a dormant state by T cells in BM, in particular by CD8-positive T cells.

Minimal Residual Disease in Gastric Cancer: Evidence of an Independent Prognostic Relevance of Urokinase Receptor Expression by Disseminated Tumor Cells in the Bone Marrow

2002 ◽  
Vol 20 (8) ◽  
pp. 2005-2016 ◽  
Author(s):  
Markus Maria Heiss ◽  
Erich H. Simon ◽  
Bianca C.M. Beyer ◽  
Klaus Uwe Gruetzner ◽  
Anwar Tarabichi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
Overall Survival ◽  
Tumor Cells ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Disseminated Tumor Cells ◽  
Primary Surgery ◽  
Disease Free ◽  
Minimal Residual

PURPOSE: To study the invasion-related molecule urokinase-type plasminogen activator receptor (u-PAR) expressed by disseminated tumor cells as a biologic predictor of poor survival in a large prospective series of patients with gastric cancer. PATIENTS AND METHODS: In 156 gastric cancer patients (prospective series), disseminated tumor cells in the bone marrow and the u-PAR expressed by these tumor cells were determined by cytokeratin (CK) 18 immunocytochemistry and u-PAR/CK18 double immunocytochemistry. RESULTS: In contrast to the mere detection of disseminated tumor cells at primary surgery, the additional evidence of u-PAR on these cells correlated significantly with pathologic T stage (P = .0474) and the expression of u-PAR (P = .0093) and plasminogen-activator inhibitor 1 (P = .0145) in the primary tumor (immunohistochemistry, χ2). Kaplan-Meier analysis revealed no association with prognosis for the mere detection of disseminated tumor cells. In contrast, a significant association was seen between detection of u-PAR on these cells and shorter disease-free (P < .0001) and overall survival (P < .0001). Multivariate analysis revealed that u-PAR on disseminated tumor cells at the time of primary surgery is an independent prognostic factor for disease-free (95% confidence interval [CI], 1.72 to 3.21; P = .024) and overall survival (P = .0049; relative risk, 2.89; 95% CI, 1.92 to 4.30). CONCLUSION: This is the first large study to show that u-PAR, detected on disseminated tumor cells in the bone marrow, is an independent prognostic parameter in gastric cancer, in contrast to the mere detection of minimal residual disease (MRD). u-PAR may be a promising marker to define a critical subpopulation of disseminated tumor cells and a target to eliminate MRD. Molecular phenotyping of MRD is critical for defining its individual clinical relevance.

scholarly journals Impact of Palliative Gastrectomy in Patients with Incurable Gastric Cancer

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 198
Author(s):  
Ji Yeon Park ◽  
Byunghyuk Yu ◽  
Ki Bum Park ◽  
Oh Kyoung Kwon ◽  
Seung Soo Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Resection ◽  
Palliative Resection ◽  
Primary Tumors ◽  
Palliative Intent ◽  
Palliative Gastrectomy ◽  
Gastric Cancer Patients ◽  
The Impact

Background and Objectives: The prognosis of metastatic or unresectable gastric cancer is dismal, and the benefits of the palliative resection of primary tumors with noncurative intent remain controversial. This study aimed to evaluate the impact of palliative gastrectomy (PG) on overall survival in gastric cancer patients. Materials and Methods: One hundred forty-eight gastric cancer patients who underwent PG or a nonresection (NR) procedure between January 2011 and 2017 were retrospectively reviewed to select and analyze clinicopathological factors that affected prognosis. Results: Fifty-five patients underwent primary tumor resection with palliative intent, and 93 underwent NR procedures owing to the presence of metastatic or unresectable disease. The PG group was younger and more female dominant. In the PG group, R1 and R2 resection were performed in two patients (3.6%) and 53 patients (96.4%), respectively. The PG group had a significantly longer median overall survival than the NR group (28.4 vs. 7.7 months, p < 0.001). Multivariate analyses revealed that the overall survival was significantly better after palliative resection (hazard ratio (HR), 0.169; 95% confidence interval (CI), 0.088–0.324; p < 0.001) in patients with American Society of Anesthesiologists Physical Status (ASA) scores ≤1 (HR, 0.506; 95% CI, 0.291–0.878; p = 0.015) and those who received postoperative chemotherapy (HR, 0.487; 95% CI, 0.296–0.799; p = 0.004). Among the patients undergoing palliative resection, the presence of <15 positive lymph nodes was the only significant predictor of better overall survival (HR, 0.329; 95% CI, 0.121–0.895; p = 0.030). Conclusions: PG might lead to the prolonged survival of certain patients with incurable gastric cancer, particularly those with less-extensive lymph-node metastasis.

Perioperative Activation of Disseminated Tumor Cells in Bone Marrow of Patients With Prostate Cancer

2009 ◽  
Vol 27 (10) ◽  
pp. 1549-1556 ◽  
Author(s):  
Dorothea Weckermann ◽  
Bernhard Polzer ◽  
Thomas Ragg ◽  
Andreas Blana ◽  
Günter Schlimok ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Cox Regression ◽  
Systemic Disease ◽  
Disseminated Tumor Cells ◽  
Comparative Genomic ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
Cox Regression Analysis

Purpose The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease. Patients and Methods Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization. Results Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis. Conclusion Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.

Clinical Relevance of Occult Tumor Cells in Lymph Nodes From Gastric Cancer Patients

2005 ◽  
Vol 29 (9) ◽  
pp. 1135-1144 ◽  
Author(s):  
Fania S Doekhie ◽  
Wilma E Mesker ◽  
J Han J. M. van Krieken ◽  
Niels F. M Kok ◽  
Henk H Hartgrink ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Clinical Relevance ◽  
Occult Tumor ◽  
Gastric Cancer Patients ◽  
Occult Tumor Cells

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.

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