scholarly journals Pooled Analysis of the Prognostic Relevance of Disseminated Tumor Cells in the Bone Marrow of Patients With Ovarian Cancer

2013 ◽  
Vol 23 (5) ◽  
pp. 839-845 ◽  
Author(s):  
Tanja Fehm ◽  
Malgorzata Banys ◽  
Brigitte Rack ◽  
Wolfgang Janni ◽  
Christian Marth ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Overall Survival ◽  
Confidence Interval ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
International Federation ◽  
Gynecology And Obstetrics ◽  
Resection Status

ObjectiveDetection of disseminated tumor cells (DTCs) in the bone marrow (BM) of patients with breast cancer is associated with poor outcomes. Recent studies demonstrated that DTCs may serve as a prognostic factor in ovarian cancer. The aim of this 3-center study was to evaluate the impact of BM status on survival in a large cohort of patients with ovarian cancer.Materials and MethodsFour hundred ninety-five patients with primary ovarian cancer were included in this 3-center prospective study. Bone marrow aspirates were collected intraoperatively from the iliac crest. Disseminated tumor cells were identified by antibody staining and by cytomorphology. Clinical outcome was correlated with the presence of DTCs.ResultsDisseminated tumor cells were detected in 27% of all BM aspirates. The number of cytokeratin-positive cells ranged from 1 to 42 per 2 × 106 mononuclear cells. Disseminated tumor cell status did correlate with histologic subtype but not with any of the other established clinicopathologic factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 months; 95% confidence interval, 37–65 months vs 33 months; 95% confidence interval, 23–43 months; P = 0.023). In the multivariate analysis, BM status, International Federation of Gynecology and Obstetrics stage, nodal status, resection status, and age were independent predictors of reduced overall survival, whereas only BM status, International Federation of Gynecology and Obstetrics stage, and resection status independently predicted progression-free survival.ConclusionsTumor cell dissemination into the BM is a common phenomenon in ovarian cancer. Disseminated tumor cell detection has the potential to become an important biomarker for prognostication and disease monitoring in patients with ovarian cancer.

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.

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.

Role of an EpCAM auto-antibody in ovarian cancer patients with special regard to disseminated tumor cells in bone marrow

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16557-e16557
Author(s):  
M. Heubner ◽  
S. Kasimir-Bauer ◽  
D. Errico ◽  
D. Herlyn ◽  
R. Kimmig ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
Healthy Controls ◽  
Line Treatment ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
First Line Treatment

e16557 Background: EpCAM is a tumor associated antigen which is frequently expressed in ovarian cancer. Recently, an autoantibody (AAB) against EpCAM has been identified in ovarian cancer patients. Autoantibodies are immunogene factors and might be of prognostic importance. We showed that disseminated tumor cells (DTC) in bone marrow carry the EpCAM antigen on their surface and correlate with poorer progression free survival (PFS). Here, we evaluated whether EpCAM-AABs have an impact on clinical parameters or the presence of DTC in ovarian cancer patients. Methods: EpCAM-AABs were determined in sera of 28 healthy voluntary age matched females and 62 patients with primary epithelial ovarian cancer before and after platinum-based chemotherapy using a recombinant EpCAM-epitope for antibody- detection by ELISA technique. Mean follow up time was 13 months. DTC in BM were detected by immunocytochemistry applying the pan cytokeratin antibody A45-B/B3. All samples exceeding the mean antibody titer of healthy controls plus 2 standard deviations were considered positive. Results: The antibody titer of healthy controls was 0.061 + 0.015. Using a cut-off value of 0.091, we found 9/62 (15%) ovarian cancer patients to be positive for EpCAM-AABs after first-line treatment. Interestingly, no positive AAB-titers were seen before therapy. Using the paired T-Test, we noted a significant posttherapeutic increase of AABs (CI 0.95, p < 0.0001). Analysis of PFS, FIGO stage, resection status, grading, age, sensitivity to platinum based chemotherapy and DTC did not reveal significant associations with positive EpCAM-AAB titers. Conclusions: The clinical course of ovarian cancer patients and the prevalence of DTC were not altered by EpCAM-AABs. Interestingly, we observed an increase of antibody-levels after first-line treatment. For further validation, we intend to extend our patient collective. In future, it might also be interesting to investigate the impact of AABs on response to targeted therapies against EpCAM. No significant financial relationships to disclose.

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.

Disseminated Tumor Cells in Lymph Nodes as a Determinant for Survival in Surgically Resected Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (1) ◽  
pp. 19-19 ◽  
Author(s):  
B. Kubuschok ◽  
B. Passlick ◽  
J. R. Izbicki ◽  
O. Thetter ◽  
K. Pantel
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lymph Nodes ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Increased Risk

PURPOSE: In recent years, the detection of even a few tumor cells in lymph nodes of patients with surgically resected non–small-cell lung cancer (NSCLC) became possible with immunohistochemical staining procedures. Tumor cells in lymph nodes have been shown to be associated with an increased rate of early recurrence. However, the prognostic significance of this minimal tumor cell spread for overall survival remains unclear. PATIENTS AND METHODS: We used the epithelium-specific monoclonal antibody Ber-EP4, which recognizes the 17-1A antigen (also called EGP40 or Ep-CAM), to discover small tumor cell deposits (≤ three cells) in 565 regional lymph nodes judged as tumor-free by conventional histopathology in patients with NSCLC staged as pT1-4, pN0-2, M0, R0. In a prospective analysis, we studied the influence of the detected tumor cells on the cancer recurrence rate and survival of 117 patients. RESULTS: Ber-EP4-positive cells were found in 27 of 125 patients (21.6%). After an observation period of 64 months, patients with disseminated tumor cells had reduced disease-free survival (P < .0001) and overall survival (P = .0001) rates in univariate analyses (log-rank test). Multivariate analysis (Cox model) showed a 2.7 times increased risk for tumor relapse and a 2.5 times increased risk for shorter survival in patients with disseminated tumor cells compared with patients without such cells. Patients without any evidence of histopathologic and immunohistochemical lymph node involvement had an overall survival rate of 78%. CONCLUSION: The immunohistochemical detection of disseminated tumor cells in lymph nodes of patients with completely resected NSCLC is an independent prognostic factor for overall survival.

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