Micrometastasis in the bone marrow of patients with lung cancer associated with a reduced expression of E-cadherin and β-catenin: Risk assessment by immunohistochemistry

Sugio, Kenji; Kase, Shinichiro; Sakada, Takashi; Yamazaki, Koji; Yamaguchi, Masafumi; Ondo, Kaoru; Yano, Tokujiro

doi:10.1067/msy.2002.119793

Cited by 33 publications

(19 citation statements)

References 24 publications

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“…Our results are in contrast with the experiences of Cote et al [16] , Oghami et al [17] , and Sugio et al [19] . These authors had a relatively small number of patients with stage I and II NSCLC (17,26, and 41, respectively); the disease-free interval was found to be affected by the occult tumor cells in the study by Cote et al [16] and Oghami et al [17] , while Sugio et al [19] could demonstrate only a trend, even though the overall survival was significant. Anyway, we believe that it is better to consider disease-free interval instead of overall survival, when the oncological issue is analyzed, because overall survival could be affected by disturbing factors such as age, gender, or general condition.…”

Section: Discussioncontrasting

confidence: 57%

“…Among the largest existing studies, the prevalence of occult tumor cells in the bone marrow ranges from 21.9% [14] to 59.7% [15] . Adding our data to these studies, the average prevalence in 977 patients is 34.3% [16][17][18][19] . Although different sites of probing, inhomogeneous markers and a variety of stages were considered, the prevalence of occult tumor cells did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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Objectives: This study was designed to verify the prognostic impact of occult tumor cells in the bone marrow of stage I and II non-small-cell lung cancer patients using cytokeratin as a micrometastatic marker. Methods: One hundred and fifty-two patients with stage I and II non-small-cell lung cancer, who underwent radical surgery by pulmonary lobectomy, were entered into the study. Bone marrow from fragments of resected ribs, and primary tumors were stained by anti-cytokeratin 18 antibody. Fourteen bone marrow specimens from patients without malignancy were used as a control group. Cancer recurrence was the study end point. Results: All the primary tumors were positive for cytokeratin; occult tumor cells were detected in 38 bone marrow specimens (25%). The prevalence of the occult tumor cells was not related to age, gender, tumor stage, histological differentiation or grade. The mean follow-up time was 35.3 months; 68 patients developed recurrence; the mean time for recurrence was 21.2 months. The general disease-free interval was not related to the presence of occult tumor cells in the bone marrow. This result did not change when grouping the patients by tumor stage. The stage was the best predictor of cancer recurrence (Cox proportional hazards model ratio: 2.09; p = 0.0026). Conclusions: This study confirms that immunocytochemical analysis detects occult tumor cells in the bone marrow of at least 25% of patients surgically treated for stage I and II non-small-cell lung cancer. These occult tumor cells do not have any impact on the disease-free interval.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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“…(Aoki et al 2003;Asgeirsson et al 2000;Bankfalvi et al 2002;Chow et al 2001;Ikeguchi et al 2000;Loric et al 2001;Rhodes et al 2003;Tanaka et al 2003). It is also a significantly poor prognostic factor for survival (Shnayder et al 2001;Sugio et al 2002). Examination of E-CD expression in biopsy tumor specimens may be useful for predicting micrometastasis and/or tumor cell microinvolvement (Nakajo et al 2001;Rodrigo et al 2002).…”

Section: E-cadherin and Beta-cateninsmentioning

confidence: 92%

Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature

Qin

Tang

2004

J Cancer Res Clin Oncol

173

148

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Molecular markers (biomarkers) for hepatocellular carcinoma (HCC) metastasis and recurrence could provide additional information to that gained from traditional histopathological features. A large number of biomarkers have been shown to have potential predictive significance. One important aspect of this is to detect the transcripts of tumor-associated antigens (such as AFP, MAGEs, and CK19), which are proposed as predictive markers of HCC cells disseminated into the circulation and for metastatic recurrence. Another important aspect is to analyze the molecular markers for cellular malignancy phenotype, including DNA ploidy, cellular proliferation index, cell cycle regulators, oncogenes, and tumor suppressors (especially p53 gene), as well as telomerase activity. Molecular factors involved in the process of HCC invasion and metastasis, including adhesion molecules (E-cadherin, catenins, ICAM-1, laminin-5, CD44 variants, osteopontin), proteinases responsible for the degradation of extracellular matrix (MMPs, uPA system), as well as angiogenesis regulators (such as VEGF, intratumor MVD), have also been shown to be potential predictors for HCC metastatic recurrence and clinical outcomes. One important new trend is to widely delineate biomarkers with genomic and proteomic expression with reference to predicting metastatic recurrence, molecular diagnosis, and classification, which has been drawing more attention recently. Body fluid (particularly blood and urine) testing for biomarkers is easily accessible and more useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum and its genetic alterations is another important direction. More attention should be paid to these areas in the future. As understanding of tumor biology deepens, more and more new biomarkers with high sensitivity and specificity for HCC metastatic recurrence could be found and routinely used in clinical assays. However, the combination of the pathological features and some of the biomarkers mentioned above seems to be more practical up to now.

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“…While the frequency of positive patients does not seem to correlate with the antibody used, the sampling number and also the anatomic site of BM aspirations might influence the number of positive cases. A higher frequency of DTC was not only found in BM aspirations from the rib or sternum in lung cancer patients [163][164][165] but also among breast CEA, carcinoembryonic antigen; LN, lymph node; NA, information not available; NS, not significant; ND, not determined; DFS, disease-free survival; OS, overall survival; RR, recurrance rate. Multicenter study with data collected from 15 hospitals.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…166,167 Irrespective of the localization of the BM puncture, 8 studies have shown a correlation between DTC in BM and worse clinical outcome. [163][164][165][168][169][170][171][172] However, the largest study conducted so far on 196 patients could not find an association, which can, however, be explained by a very short follow up time (median, 8 months). 173 Interestingly, very few studies have been performed using RT-PCR to detect DTC in BM.…”

Section: Disseminated Tumor Cellsmentioning

confidence: 99%

Review: Biological relevance of disseminated tumor cells in cancer patients

Riethdorf

Wikman

Pantel

2008

Intl Journal of Cancer

289

236

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The prognosis of cancer patients is largely determined by the occurrence of distant metastases. In patients with primary tumors, this relapse is mainly due to clinically occult micrometastasis present in secondary organs at primary diagnosis but not detectable even with high resolution imaging procedures. Sensitive and specific immunocytochemical and molecular assays enable the detection and characterization of disseminated tumor cells (DTC) at the single cell level in bone marrow (BM) as the common homing site of DTC and circulating tumor cells (CTC) in peripheral blood. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC. Furthermore, we will discuss data on the biology of DTC and the clinical relevance of DTC detection. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clinical relevance of DTC in patients with other carcinomas. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations. Further characterization is required to understand the biology of DTC and to identify new targets for improved risk prevention and tailoring of therapy. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States.

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Micrometastasis in the bone marrow of patients with lung cancer associated with a reduced expression of E-cadherin and β-catenin: Risk assessment by immunohistochemistry

Cited by 33 publications

References 24 publications

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

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

Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature

Review: Biological relevance of disseminated tumor cells in cancer patients

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