Detection of cancer cells disseminated in bone marrow using real-time quantitative RT-PCR of CEA, CK19, and CK20 mRNA in patients with gastric cancer

Fujita, Yoshikatsu; Terashima, Masanori; Hoshino, Yutaka; Ohtani, S.; Kashimura, Seigo; Kanzaki, Norio; Osuka, Fumihiko; Kogure, Michihiko; Gotoh, Mitsukazu

doi:10.1007/s10120-006-0398-z

Cited by 25 publications

(15 citation statements)

References 24 publications

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“…In contrast, CEA has been reported to be a reliable target for the detection of disseminated gastric cancer cells, and is the most common marker for detecting micrometastasis with RT -PCR (Kodera et al, 1998;Nakanishi et al, 2000;Osaka et al, 2004). The quantitative RT -PCR method using multiple markers reportedly improved the sensitivity and specificity of the quantitative RT -PCR method (Guller et al, 2002;Timar et al, 2002;Osaka et al, 2004;Fujita et al, 2006). We therefore selected the combination of CEA and CK-20 as diagnostic markers for predicting micrometastasis in patients with gastric carcinoma in this study.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection

et al. 2007

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Identification of cancer cells in the peritoneal cavity could influence therapy and outcome of gastric carcinoma patients. The objective of this study was to evaluate the clinical impact of the real-time quantitative polymerase chain reaction-(PCR) based identification of isolated tumour cells in the peritoneal lavage fluid of gastric carcinoma. The peritoneal lavage fluid of 116 patients with gastric cancer was sampled at laparotomy. After RNA extraction and reverse transcription, real-time quantitative PCR was performed using the primers and probes for carcinoembryonic antigen (CEA) and cytokeratin-20 (CK20). When either the CEA mRNA or CK20 mRNA level of the sample was over the cutoff value, the sample was determined to be PCR-positive. Forty-six (40%) of the 116 patients were PCR-positive and 30 (65%) of the 46 PCR-positive patients died as a result of recurrent peritoneal dissemination. The prognosis of the 46 PCR-positive patients was significantly (Po0.001) worse than that of 70 PCR-negative patients. Furthermore, in 80 of the cases with a curative R0 resection, 15 of the patients with PCR-positive findings had a significantly (Po0.001) poorer prognosis than the 65 PCR-negative patients. The prognosis of the PCR-positive patients was significantly poorer than that of the PCR-negative patients in the T3 (Po0.0001) and T4 (P ¼ 0.048) subgroups. In a multivariate analysis of the 80 cases with a curative R0 resection, the real-time quantitative RT -PCR (CEA and/or CK20) levels indicated that they were independent prognostic factors. The real-time quantitative RT -PCR analysis of the CEA and/or CK20 transcripts in the peritoneal lavage fluid is useful for predicting the peritoneal recurrence in patients who are undergoing a curative resection for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection

et al. 2007

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“…55 A control experiment showed no cross-reactivity with murine GAPDH (Mm99999915_g1; Applied Biosystems, Foster City, CA, USA). In order to study the potential of these cells to metastasize into BM cavities, 30 days after injection, the cells were isolated from two of the legs of each mouse and their presence was examined using qRT-PCR to distinguish between human and murine cells.…”

Section: Methodsmentioning

confidence: 99%

The decreased metastatic potential of rhabdomyosarcoma cells obtained through MET receptor downregulation and the induction of differentiation

et al. 2013

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Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. The MET receptor has an important role in the biology of RMS, and its overexpression and hyperactivation correlate with the metastatic ability of RMS. Consequently, interfering with MET expression or functionality may constitute a sound strategy for reducing the progression and metastatic potential of RMS. Our study reveals that downregulation of the MET receptor leads to changes in the morphology of ARMS cell in vivo. Tumors acquire a spindle shape that is characteristic of muscle fibers. Inhibition of MET expression or function leads to (i) a decreased expression of the early myogenic marker MyoD, (ii) a decreased ability of ARMS cells to metastasize to bone marrow cavities, (iii) downregulation of CXCR4 receptor expression and (iv) a decreased migration of MET-depleted cells towards gradients of HGF and SDF-1. Finally, we demonstrate that in vitro differentiation of alveolar RMS cells decreases their metastatic behavior by reducing both the expression of the MET and CXCR4 receptors and their migratory response to HGF and SDF-1. These findings suggest that blockers of MET receptor function and inducers of RMS cells differentiation may be clinically useful for reducing the aggressiveness and metastatic potential of RMS and may have significant implications for its treatment.

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“…Cytokeratin filaments are formed by tetrameric heteropolymers of two different types of CKs (types I and II) (Chu et al, 1993). With respect to their relation with cancer, the expression levels of some CKs, such as CK19, are abundant and stable among tumours, therefore these molecules are considered useful markers for micrometastases or speculation on occult primary cancer (Fujita et al, 2006;Liu et al, 2008). On the other hand, CK expression levels are reported to change dynamically with carcinogenesis, at least in some cases.…”

Section: Discussionmentioning

confidence: 99%

Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus

et al. 2009

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BACKGROUND: Cytokeratins (CKs) are structural marker proteins specific for epithelial cells. However, recent studies indicate their involvement in cancer progression. METHODS: We evaluated CK18 and its filament partner, CK8 expression, by immunohistochemistry in 210 resected specimens from patients with oesophageal squamous cell carcinoma (OSCC). We also analysed the relationship between their expression and various clinicopathological parameters including prognosis. RESULTS: Neither CK18 nor CK8 was expressed in non-cancerous squamous epithelium whereas proper oesophageal glands expressed both CKs. Ninety (42.9%) tumours were CK18 positive and 85 (40.5%) CK8 positive, and the concordance rate for immunohistochemical classification for CK18 and CK8 was 82.4%. CK18 expression correlated with poorly differentiated tumours, use of neo-adjuvant chemotherapy, and advanced stage. Prognosis of patients with CK18-positive tumours was poorer than that of patients with negative OSCC (Po0.001). A similar trend was noted for CK8 expression. Multivariate analysis identified pT (P ¼ 0.020), pN number (P ¼ 0.001), and CK18 expression (P ¼ 0.004) as independent prognostic factors. CK18 expression in 83 pretreatment biopsy specimens was detected in 47 cases (56.6%) and also correlated with prognosis (P ¼ 0.045). CONCLUSION: CK18/CK8 expression correlated with progression of OSCC. The significant correlation with prognosis and stable expression in biopsy specimen suggest usefulness of CK18 in selection of treatment strategies for OSCC.

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Detection of cancer cells disseminated in bone marrow using real-time quantitative RT-PCR of CEA, CK19, and CK20 mRNA in patients with gastric cancer

Abstract: The incidence of disseminated cancer cells in bone marrow in our study appears low, unlike that in previous reports. The significance of disseminated cancer cells in bone marrow may also be quite low in gastric cancer.

Cited by 25 publications

References 24 publications

Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection

Prognostic impact of PCR-based identification of isolated tumour cells in the peritoneal lavage fluid of gastric cancer patients who underwent a curative R0 resection

The decreased metastatic potential of rhabdomyosarcoma cells obtained through MET receptor downregulation and the induction of differentiation

Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus

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