Micrometastatic tumour cells in bone marrow of patients with gastric cancer: Methodological aspects of detection and prognostic significance

Schlimok, Günter; Funke, I.; Pantel, Klaus; Strobel, Friedrich; Lindemann, Fritz; Witte, Jens; Riethmüller, Gert

doi:10.1016/0277-5379(91)90032-9

Cited by 161 publications

(81 citation statements)

References 21 publications

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“…While statistically significant correlations with undifferentiated histology and/or more advanced depth of tumour invasion were found in some studies (Schlimok et al, 1991;O'Sullivan et al, 1995;Maehara et al, 1996;, in others Jauch et al, 1996;Schott et al, 1998;Bonavina et al, 2001), as well in ours, there was no correlation.…”

Section: Cytokeratin-positive Cells In Bone Marrow Of Gastric Cancer supporting

confidence: 42%

“…Clinical outcome in gastric cancer has been reported to be affected by the presence of bone marrow infiltration in two studies (Schlimok et al, 1991;Jauch et al, 1996). While in the report by Schlimok et al, 1991 only 38 R0 patients were evaluated, in the recent study by Jauch et al, 1996, the survival was analysed in 109 R0 patients.…”

Section: Cytokeratin-positive Cells In Bone Marrow Of Gastric Cancer mentioning

confidence: 99%

“…While in the report by Schlimok et al, 1991 only 38 R0 patients were evaluated, in the recent study by Jauch et al, 1996, the survival was analysed in 109 R0 patients. In the latter study, the detection of more than three tumour cells in bone marrow was associated with poorer survival particularly in N0 and T1/T2 subsets.…”

Section: Cytokeratin-positive Cells In Bone Marrow Of Gastric Cancer mentioning

confidence: 99%

“…Bone marrow micrometastases have been found in over onequarter of patients undergoing curative resection of gastrointestinal cancer (O'Sullivan et al, 1995) and according to some authors they affected prognosis (Schlimok et al, 1991;Jauch et al, 1996). However the independent prognostic significance of isolated tumour cells in bone marrow is still a matter of debate and remains to be substantiated (Funke and Schraut, 1998;Hermanek et al, 1999).…”

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The presence of bone marrow cytokeratin-immunoreactive cells does not predict outcome in gastric cancer patients

et al. 2002

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The independent prognostic significance of isolated tumour cells in bone marrow is still a matter of debate. This study evaluated the possible association of bone marrow micrometastases with tumour progression and prognosis in patients affected by gastric cancer. Bone marrow aspirates from both iliac crests were obtained from 114 consecutive patients operated on for gastric cancer. The specimens were stained with monoclonal antibody CAM 5.2 which reacts predominantly with cytokeratin filaments 8 and 19. Among 114 cases analysed, 33 cases (29%) had cytokeratine-positive cells in the bone marrow. There was no significant relationship between the presence of bone marrow micrometastases and site, depth of tumour invasion, lymph node metastases, presence of metastases. Patients with cytokeratine-positive cells had a trend towards a diffuse type histology (P=0.06). Among the 88 curatively resected patients, median survivals were 40 months and 36 months for cytokeratine-negative and cytokeratine-positive subsets respectively (P=0.9). Recurrence of the disease was observed in 39 cases (44.3%); 11 of 24 (45.8%) in the cytokeratine-positive subset and 28 of 64 (43.7%) in the cytokeratine-negative subset. In conclusion in our experience the presence of cytokeratine-positive cells in the bone marrow of curatively resected gastric cancer patients did not affect outcome and its independent prognostic significance remains to be proven before its official acceptance in the TNM classification.

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Section: Cytokeratin-positive Cells In Bone Marrow Of Gastric Cancer supporting

confidence: 42%

Section: Cytokeratin-positive Cells In Bone Marrow Of Gastric Cancer mentioning

confidence: 99%

Section: Cytokeratin-positive Cells In Bone Marrow Of Gastric Cancer mentioning

confidence: 99%

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confidence: 99%

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The presence of bone marrow cytokeratin-immunoreactive cells does not predict outcome in gastric cancer patients

et al. 2002

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“…Second, in the setting of autologous bone marrow transplantation (ABMT) or peripheral stem cell reinfusion after high-dose chemotherapy, contamination of the reinfused bone marrow or stem cell population with tumour cells might worsen prognosis (Anderson et al, 1989;Gribben et al, 1991;Brenner et al, 1993;Brugger et al, 1994;Moss et al, 1994). In recent years, especially in breast and colon cancer, it has been shown that occult contamination of the peripheral blood or bone marrow at diagnosis with tumour cells exerts an adverse influence on survival (Berger et al, 1988;Cote et al, 1991;Schlimok et al, 1991;Pantel et al, 1993;Diel et al, 1994;Harbeck et al, 1994;Menard et al, 1994). Often, in these studies, a monoclonal antibody (MAb) or a panel of MAbs directed against tumour cell-surface glycoproteins or cytokeratins was used to detect circulating tumour cells.…”

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confidence: 99%

A quantitative reverse transcriptase polymerase chain reaction-based assay to detect carcinoma cells in peripheral blood

Helfrich¹,

tenPoele²,

Meersma³

et al. 1997

Br J Cancer

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Summary The presence of tumour cells in the circulation may predict disease recurrence and metastasis. To improve on existing methods of cytological or immunocytological detection, we have developed a sensitive and quantitative technique for the detection of carcinoma cells in blood, using the reverse transcriptase polymerase chain reaction (RT-PCR) identifying transcripts of the pancarcinoma-associated tumour marker EGP-2 (KSA or 17-lA antigen). The amount of EGP2 mRNA was quantified using an internal recombinant competitor RNA standard with known concentration and which is both reversely transcribed and co-amplified in the same reaction, allowing for a reliable assessment of the initial amount of EGP2 mRNA in the sample. Calibration studies, seeding blood with MCF-7 breast carcinoma cells, showed that the assay can detect ten tumour cells among 1.0 x 106 leucocytes. The PCR assay revealed that normal bone marrow expresses low levels of EGP2 mRNA, although immunocytochemistry with the anti-EGP2 MAb MOC31 could not identify any positively stained cell. Analyses using this RT-PCR assay may prove to have applications to the assessment of circulating tumour cells in clinical samples.

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Immunocytochemical detection of isolated epithelial cells in bone marrow: non-specific staining and contribution by plasma cells directly reactive to alkaline phosphatase

et al. 1998

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Detection of isolated tumour cells (TCs) in bone marrow (BM) from epithelial cancer patients by immunocytochemical (ICC) analysis seems to predict future relapse, but the reported percentages of positive BMs among patients with localized cancer show large variations and the number of detected TCs is low. This emphasizes the importance of thoroughly testing the methods in use. This study was performed to clarify to what extent positive staining of haematopoietic cells (HCs) interferes with the ICC detection of epithelial cells in BM. BM mononuclear cells (MNCs) from normal donors and stage I–II breast cancer patients were stained with anti‐cytokeratin (CK) and isotype control monoclonal antibodies (MAbs) followed by alkaline phosphatase (AP)‐based visualization of immunolabelled cells. In the ICC staining of normal donors by the anti‐CK MAbs AE1/AE3 or A45‐B/B3, rare immunoreactive cells were detected in 7/20 and 8/19 BMs, respectively. Morphological examination recognized all these cells as typical HCs. In the breast cancer patients (n=257), anti‐CK‐positive cells were detected in 26·6 per cent, excluding cells with HC morphology. Using the same morphological criteria, isotype control‐positive cells were detected in 5·4 per cent of patients. Some of the false‐positive events were further analysed and cells with strong reactivity against the AP enzyme alone were detected. Double ICC staining recognized the majority of these AP directly‐reactive cells as CD45‐negative and human Ig kappa/lambda‐positive, in accordance with the phenotype of mature plasma cells. Morphological evaluation and adequate controls are important to ensure the diagnostic specificity of micrometastases in BM. It is recommended that the number of BM MNCs included in negative controls should equal the number of cells in the diagnostic specimens. © 1998 John Wiley & Sons, Ltd.

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Micrometastatic tumour cells in bone marrow of patients with gastric cancer: Methodological aspects of detection and prognostic significance

Cited by 161 publications

References 21 publications

The presence of bone marrow cytokeratin-immunoreactive cells does not predict outcome in gastric cancer patients

The presence of bone marrow cytokeratin-immunoreactive cells does not predict outcome in gastric cancer patients

A quantitative reverse transcriptase polymerase chain reaction-based assay to detect carcinoma cells in peripheral blood

Immunocytochemical detection of isolated epithelial cells in bone marrow: non-specific staining and contribution by plasma cells directly reactive to alkaline phosphatase

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