Immunocytochemical Detection of Occult Tumor Cells in the Bone Marrow: Prognostic Impact on Early Stages of Lung Cancer

2008 ◽  
Vol 41 (3) ◽  
pp. 267-271 ◽  
Author(s):  
M. Nosotti ◽  
D. Tosi ◽  
A. Palleschi ◽  
L. Rosso ◽  
P. Mendogni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Prognostic Impact ◽  
Occult Tumor ◽  
Early Stages ◽  
Immunocytochemical Detection ◽  
Occult Tumor Cells

Increased Risk of Systemic Relapses Associated With Bone Marrow Micrometastasis and Circulating Tumor Cells in Localized Ewing Tumor

2003 ◽  
Vol 21 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Gudrun Schleiermacher ◽  
Martine Peter ◽  
Odile Oberlin ◽  
Thierry Philip ◽  
Hervé Rubie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Rt Pcr ◽  
Occult Tumor ◽  
Relapse Pattern ◽  
Localized Disease ◽  
Occult Tumor Cells ◽  
Pcr Targeting ◽  
Ewing Tumor

Purpose: The presence of metastasis is a major prognostic factor in Ewing tumor (ET). The relapse pattern of patients with localized tumors has long indicated that cases with disseminated ET cells escape detection at diagnosis. ET cells are characterized by specific gene fusions that can be detected with high sensitivity and specificity by reverse transcriptase polymerase chain reaction (RT-PCR). Patients and Methods: RT-PCR targeting EWS-FLI-1 or EWS-ERG transcripts was used to search for occult tumor cells in peripheral blood (PB) and bone marrow (BM) at diagnosis in 172 patients with ET, and the prognostic significance of this parameter was assessed. Results: As we suggested previously in a smaller series of patients, RT-PCR positivity of the BM was correlated with a high risk of adverse outcome in the overall study population (P = .007). More interestingly, among patients with otherwise localized tumors, BM micrometastasis also predicted significantly poorer disease-free survival rates (P = .043). The presence of circulating tumor cells (CTC) was more frequently observed in patients with large tumors (P = .006). CTC were associated with a poor outcome among patients with clinically localized disease (P = .045). Patients with clinically localized disease and peripheral occult tumor cells as evidenced by BM and/or PB RT-PCR positivity had axial or proximal tumors and experienced relapses at a systemic rather than at a local level. Conclusion: Patients with localized ET and BM micrometastasis or CTC are comparable to patients with metastases in terms of the localization of the primary tumor, outcome, and relapse pattern.

scholarly journals Comparison of the clinical significance of occult tumor cells in blood and bone marrow in breast cancer

2005 ◽  
Vol 118 (8) ◽  
pp. 2013-2019 ◽  
Author(s):  
Gro Wiedswang ◽  
Elin Borgen ◽  
Cecilie Schirmer ◽  
Rolf Kåresen ◽  
Gunnar Kvalheim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Clinical Significance ◽  
Occult Tumor ◽  
Occult Tumor Cells

Prognostic Impact of Micrometastatic Tumor Cells in the Lymph Nodes and Bone Marrow of Patients With Completely Resected Stage I Non–Small-Cell Lung Cancer

2002 ◽  
Vol 20 (13) ◽  
pp. 2930-2936 ◽  
Author(s):  
Toshihiro Osaki ◽  
Tsunehiro Oyama ◽  
Chun-Dong Gu ◽  
Toshihiro Yamashita ◽  
Tomoko So ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Marrow ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Small Cell ◽  
Stage I ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Resected Stage ◽  
Nsclc Patients

PURPOSE: This study was designed to substantiate the prognostic impact of occult micrometastatic tumor cells in the lymph nodes (LNs) and bone marrow (BM) in stage I non–small-cell lung cancer (NSCLC) patients using cytokeratin (CK) as a micrometastatic marker and the relationship between the micrometastases in the LNs and BM. PATIENTS AND METHODS: A total of 2,432 hilar and mediastinal LNs were removed during surgery from 115 patients with completely resected stage I NSCLC. The LNs were analyzed for micrometastasis using immunohistochemistry with the biclonal anti-CK antibody AE1/AE3. BM aspirates from 115 patients were immunocytochemically stained with the monoclonal anti-CK antibody CK2. RESULTS: CK-positive (CK+) cells were detected in 42 (1.7%) of 2,432 LNs, in 32 (27.8%) of 115 patients, and in 32 (27.8%) of 115 BM aspirates. There was no relationship between the frequencies of CK+ cells in the LNs and in the BM. The patients with CK+ cells in the LNs had a poor prognosis by both univariate (P = .008) and multivariate analyses (P = .01), whereas the presence of CK+ cells in the BM did not allow prediction of survival (P = .32). The prognostic impact of LNs micrometastasis was independent even after adjusting for the status of BM micrometastasis. CONCLUSION: The detection of lymph nodal micrometastatic tumor cells provides an accurate assessment of tumor staging and has powerful prognostic implications for completely resected stage I NSCLC patients.

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.

901 Single disseminated tumor cells in bone marrow and PBSC in patients with small cell lung cancer

Lung Cancer ◽  
1997 ◽  
Vol 18 ◽  
pp. 229-230
Author(s):  
U. Seifart ◽  
S. Henrich ◽  
G. Jaques ◽  
C. Loechelt ◽  
A. Wachtel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Marrow ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Cell Lung Cancer ◽  
Disseminated Tumor Cells ◽  
Small Cell ◽  
Small Cell Lung

A New Approach to Phenotyping Disseminated Tumor Cells: Methodological advances and Clinical Implications

2000 ◽  
Vol 15 (1) ◽  
pp. 100-104 ◽  
Author(s):  
F. Noack ◽  
M. Schmitt ◽  
J. Bauer ◽  
D. Helmecke ◽  
W. Krüger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Laser Scanning ◽  
Simultaneous Detection ◽  
Disseminated Tumor Cells ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Prognostic Impact ◽  
Primary Therapy ◽  
Double Immunofluorescence

At the time of primary therapy (surgery, systemic chemotherapy and/or radiation), disseminated tumor cells in the bone marrow can be found in almost one-third of patients with cancer of the breast, ovary, esophagus, stomach, colon, and other solid tumors. Whereas the prognostic impact of the mere presence of these cells is still a matter of debate, it has been shown that expression of tumor-associated antigens in disseminated tumor cells is linked to more aggressive disease. Therefore, further characterization of disseminated tumor cells at the protein and gene level has become increasingly important. To date, the most common detection method for disseminated tumor cells in the bone marrow is an immunocytochemical approach using cytokeratin-directed antibodies for detection of epithelial cells and the APAAP system for their visualization. We have established a new double immunofluorescence technique enabling simultaneous detection, phenotyping, and antigen quantification of disseminated tumor cells. Mononuclear cells from bone marrow are enriched by Ficoll gradient centrifugation and cytospins are prepared. Double immunofluorescence is performed using antibodies against cytokeratins 8/18/19 (mAb A45B/B3) and the uPA receptor CD87 (pAb HU277). CD87 expression is recorded by confocal laser scanning microscopy (CLSM) using fluorescence labeled latex beads as the reference; staining intensities of all the scans are then summed and quantified (extended focus). This protocol, originally designed for disseminated tumor cells in bone marrow, can also be applied to disseminated tumor cells in blood, to leukapheresis cells or to cells present in malignant ascites or other malignant effusions. The tumor cells detected may be used for gene and mRNA analyses. Furthermore, disseminated tumor cells also represent interesting targets for clinical studies on patient prognosis or prediction of therapy response as well as for specific tumor-biological therapies.

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