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 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.

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 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.

Use of disseminated tumor cells to predict outcome in patients with stage I-III breast cancer.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 119-119
Author(s):  
Sarah Marie Gainer ◽  
Savitri Krishnamurthy ◽  
Anirban Bhattacharyya ◽  
Ashutosh Lodhi ◽  
Carolyn S. Hall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Overall Survival ◽  
Tumor Cells ◽  
Independent Predictor ◽  
Metastatic Breast ◽  
Disseminated Tumor Cells ◽  
Stage I ◽  
Cancer Center ◽  
Tertiary Cancer Center

119 Background: Published studies from Europe have shown the presence of disseminated tumor cells (DTCs) to independently predict outcomes in patients with non-metastatic breast cancer. The purpose of this study was to assess the experience with DTCs at a tertiary cancer center and to see if these cells indeed predict outcomes in patients with stage I-III breast cancer. Methods: Clinical stage I-III breast cancer patients seen at a single tertiary cancer center provided consent to participate in an IRB-approved study involving collection of bone marrow (5 ml x 2 tubes) at the time of surgery for their primary breast cancer. DTCs were assessed by anti-CK antibody cocktail (AE1/AE3, CAM5.2, MNF 116, CK 8 and 18) following cytospin. A positive result was defined as the presence of one or more cells per 5 ml of bone marrow. Statistical analyses used chi-square and Fischer’s exact tests. Results: Three hundred and sixty-six patients were prospectively enrolled. Mean age was 53 years. Median follow-up was 32 months. DTCs were identified in 109 patients (30%). Ten percent of patients with DTCs (11/109) and 3% of patients without DTCs (8/257) died (p = 0.009). Overall survival (OS) in patients with DTCs was 30 months vs. 31 months in those without DTCs. DTCs did not predict relapse free survival (P=NS). On multivariate analysis the presence of DTCs was an independent predictor of worse overall survival (p < 0.0001). No correlation was observed between the presence of DTCs and lymph node metastases and/or other clinicopathologic variables. Conclusions: The presence of DTCs was an independent predictor of worse OS in patients with stage I-III breast cancer. Consideration should be given to the utilization of DTCs as predictors of outcome in clinical practice.

Detection of disseminated tumor cells in bone marrow as an independent prognostic factor in primary ovarian cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5042-5042
Author(s):  
Pauline Wimberger ◽  
Malgorzata Banys ◽  
Sabine Kasimir-Bauer ◽  
Andreas D. Hartkopf ◽  
Natalia Krawczyk ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
Stem Cell Marker ◽  
Primary Ovarian Cancer

5042 Background: Detection of disseminated tumor cells (DTC) in the bone marrow (BM)of breast cancer patients is associated with poor outcome. Recent studies demonstratedthat DTC may serve as a prognostic factor in ovarian cancer.The aim of our study was to evaluate the impact of BM status on survival in a large cohort of ovarian cancer patients. Methods: 365 patients with primary ovarian cancer were included into this three-center prospective study. BM aspirates were collected preoperatively from iliac crest. Disseminatedtumor cells were identified by immunocytochemistry using the pancytokeratin antibodyA45B/B3 and by cytomorphology. Patient outcomes were evaluated using a multivariable Cox regression model. Results: Disseminated tumor cells were detected in 28% of all BM aspirates. The number of CK-positive cells ranged from 1 to 42 per 2x106 mononuclear cells. DTC status did not correlate with any of the established clinicopathogical factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 mo, 95% CI: 35 – 67 mo versus 32 mo, 95% CI: 22 – 42 mo; p = 0.003). However, disease-free survival was not related to DTC-positivity. In the multivariable analysis, BM status, FIGO stage, nodal status, resection status and age were independent predictors of reduced overall survival. Interestingly, a subset of DTCs may have stem cell properties since a subset of these cells (128 out of 228 cases) were SOX2 positive, which is an embryonic stem cell marker. Conclusions: Tumor cell dissemination into bone marrow is a common phenomenon in ovarian cancer. DTC detection has the potential to become an important biomarker for prognostication and may be included as a therapeutic target in future concepts.

Prognostic significance of bone marrow micrometastases in patients with gastric cancer.

1996 ◽  
Vol 14 (6) ◽  
pp. 1810-1817 ◽  
Author(s):  
K W Jauch ◽  
M M Heiss ◽  
U Gruetzner ◽  
I Funke ◽  
K Pantel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Bone Marrow ◽  
Multivariate Analysis ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Systemic Disease ◽  
Disseminated Tumor Cells ◽  
Cell Dissemination ◽  
Disease Free

BACKGROUND Monoclonal antibodies (mabs) against components of the cytoskeleton such as cytokeratins allow single disseminated epithelial carcinoma cells to be detected in the bone marrow. The aim of this study was to examine the prognostic relevance of these cells in patients with gastric cancer and to evaluate by multivariate analysis their predictive value compared with conventional risk factors. PATIENTS AND METHODS A total of 1 x 10(6) cells from bone marrow aspirates were screened immunoctochemically for the presence and absolute number of disseminated tumor cells using mab CK2 to cytokeratin component no. 18. Patients were monitored prospectively for 30.6 +/- 15.2 months. RESULTS Between one and 122 CK2-positive cells per 1 million mononuclear bone marrow cells were present in 95 of 180 patients (53%). A similar prevalence of 51% was found in curatively operated patients (55 of 109). Comparison with conventional prognostic risk factors showed a correlation of cell dissemination with pathohistologic tumor (pT) stage (P = .07) and Bormann classification (P = .022). Tumor-cell content in the bone marrow predicted disease-free and overall survival in curatively resected patients (P = .007 and P = .049, respectively). Multivariate analysis, which included established risk factors, showed that extent of tumor-cell dissemination was an independent prognostic parameter for disease-free survival in T1/2 tumors (P = .014; relative risk [RR], 1.84; 95% confidence interval [CI], 1.35 to 2.52), in intestinal type carcinomas according to Laurén (P = .008; RR, 1.62; 95% CI, 1.23 to 2.12), and in patients without lymph node involvement (P = .004; RR, 2.43; 95% CI, 1.22 to 4.82). CONCLUSION Presence of disseminated tumor cells in bone marrow is indicative of systemic disease even in early-stage gastric cancer. The extent of tumor-cell presence in bone marrow correlates with prognosis in curatively resected patients. Therefore, a positive bone marrow finding may be a selection criteria for adjuvant treatment because of minimal residual tumor load.

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