Detection of tumor cells in peripheral blood samples from patients with germ cell tumors using immunocytochemical and reverse transcriptase-polymerase chain reaction techniques

Hildebrandt, M.; Bläser, F; Beyer, Jörg; Siegert, W.; Mapara, MY; Huhn, D.; Salama, Abdulgabar

doi:10.1038/sj.bmt.1701416

Cited by 15 publications

(7 citation statements)

References 12 publications

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“…Therefore, these tumors present with very heterogeneous expression patterns of germ cell and epithelial cell-specific proteins. Not surprisingly, the only previously published immunocytochemical CTC analysis in patients with GCTs using the pan-anti-keratin antibody A45-B/B3 only identified 3 of 20 (15%) patients with advanced and/or relapsed GCTs as positive for CTCs (10). In our study, we performed an immunocytochemical analysis applying a combination of novel germ cellspecific (anti-SALL4, anti-OCT3/4) and epithelial cellspecific (anti-keratin, anti-EpCAM) antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…These are the first 2 keratins expressed during mouse embryogenesis and might be expressed by seminomas and embryonal carcinomas (17)(18)(19)(20). Keratin 19 as a marker for epithelial cells was found to be present in some seminomas and the majority of nonseminomas (10). Furthermore, EpCAM is a homophilic, calcium-independent cell adhesion molecule and is uniquely expressed in germline and spermatogonial stem cells (21,22).…”

Section: Introductionmentioning

confidence: 99%

“…However, little is known about the presence of CTCs in blood of patients with GCTs. Few studies have previously assessed presence of tumor-specific mRNA or whole cells in apheresis products of patients undergoing peripheral stem cell transplants (9)(10)(11). In addition, in a small number of studies, putative CTCs in peripheral blood of patients with testicular GCTs were detected by reverse transcriptase PCR (RT-PCR) using AFP and human chorionic gonadotropinspecific mRNA as markers (12,13).…”

Section: Introductionmentioning

confidence: 99%

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Circulating Tumor Cells in Patients with Testicular Germ Cell Tumors

Nastały¹,

Ruf

Becker

et al. 2014

Clinical Cancer Research

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Purpose: Germ cell tumors (GCTs) represent the most frequent malignancies among young men, but little is known about circulating tumor cells (CTCs) in these tumors. Considering their heterogeneity, CTCs were investigated using two independent assays targeting germ cell tumor and epithelial cell-specific markers, and results were correlated with disease stage, histology, and serum tumor markers.Experimental Design: CTCs were enriched from peripheral blood (n ¼ 143 patients) and testicular vein blood (TVB, n ¼ 19 patients) using Ficoll density gradient centrifugation. For CTC detection, a combination of germ cell tumor (anti-SALL4, anti-OCT3/4) and epithelial cell-specific (anti-keratin, anti-EpCAM) antibodies was used. In parallel, 122 corresponding peripheral blood samples were analyzed using the CellSearch system.Results: In total, CTCs were detected in 25 of 143 (17.5%) peripheral blood samples, whereas only 11.5% of patients were CTC-positive when considering exclusively the CellSearch assay. The presence of CTCs in peripheral blood correlated with clinical stage (P < 0.001) with 41% of CTC positivity in patients with metastasized tumors and 100% in patients with relapsed and chemotherapy-refractory disease. Histologically, CTC-positive patients suffered more frequently from nonseminomatous primary tumors (P < 0.001), with higher percentage of yolk sac (P < 0.001) and teratoma (P ¼ 0.004) components. Furthermore, CTC detection was associated with elevated serum levels of a-fetoprotein (AFP; P ¼ 0.025), b-human chorionic gonadotropin (bHCG; P ¼ 0.002), and lactate dehydrogenase (LDH; P ¼ 0.002). Incidence and numbers of CTCs in TVB were much higher than in peripheral blood.Conclusions: The inclusion of germ cell tumor-specific markers improves CTC detection in GCTs. CTCs occur frequently in patients with more aggressive disease, and there is a gradient of CTCs with decreasing numbers from the tumor-draining vein to the periphery.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating Tumor Cells in Patients with Testicular Germ Cell Tumors

Nastały¹,

Ruf

Becker

et al. 2014

Clinical Cancer Research

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“…Within the context of these investigations, it became apparent that the detection of circulating tumor cells in PBPC by a reverse transcriptase polymerase chain reaction (RT-PCR) was associated with an increased relapse rate and an advanced tumor stage. In 1998, Hildebrandt et al [53] detected circulating tumor cells in autologous PBPC in TGCT patients by immunohistochemical and RT-PCR techniques.…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

Molecular Markers in Testicular Germ Cell Tumors – Objects of Clinical Research or Close to Becoming Clinical Tools?

Schrader

Heicappell²,

Müller³

et al. 2001

Oncol Res Treat

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The aim of this short review is to critically evaluate hitherto investigated molecular markers for testicular germ cell tumors. Molecular parameters have been clinically established as diagnostic and prognostic markers for a number of tumors; this has not yet been achieved for germ cell tumors. There are interesting prospects, however. Studies on the ribonucleoprotein telomerase, for example, have demonstrated a correlation between enzyme activity and chemotherapeutic drug sensitivity. Moreover, innovative treatment approaches target this reverse transcriptase via telomerase antisense RNA. Another potential diagnostic marker is the detection of circulating tumor cells, which correlated with an increased relapse rate in initial studies. There are also interesting possibilities for the germ-cell-tumor-specific isochromosome [i(12)p], which is helpful in the differential diagnosis of mediastinal masses. Here initial studies demonstrated a correlation between the copy number and resistance against chemotherapeutic drugs. Without prospective studies to validate data obtained thus far, neither these nor other parameters can be assessed as diagnostic and prognostic factors. Irrespective of their immediate clinical applicability, however, investigations on molecular alterations in testicular germ cell tumors will become the basis for a molecular-diagnostically oriented subclassification of tumors as well as for novel therapeutic approaches.

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“…Occult tumor cells in PBPC may directly contribute to relapse or may be an important predictor for rapid recurrence after myeloablative chemotherapy in patients with ovarian cancer. Several studies have recently shown that PBPC may contain residual tumor cells in hematologic malignancies (1–5) and some solid tumors (6–15). However, the issue of potential tumor contamination in the infused product has not been well studied in PBPC for patients with ovarian cancer.…”

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confidence: 99%