Detection of occult metastases in lung carcinomas: Progress and implications for lung cancer staging

Côté, Richard J.; Hawes, Debra; Chaiwun, Benjaporn; Beattie, Edward J.

doi:10.1002/(sici)1096-9098(199812)69:4<265::aid-jso12>3.0.co;2-7

Cited by 37 publications

(16 citation statements)

References 42 publications

(66 reference statements)

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“…Detection of metastatic sites that are clusters of less than 10 9 malignant cells by those imaging techniques is impossible. In recent years, many immunological and molecular techniques were introduced that have enabled progress in the detection and characterization of occult, disseminated groups of malignant cells (4,5,6,12,14).…”

Section: Discussionmentioning

confidence: 99%

“…Micrometastases are detected in the bone marrow in 20-40% of patients with operable breast cancer and in 20-70% of patients with distant metastases (5). Recent reports analyze the presence of micrometastases in the bone marrow in patients with operable NSCLC (1, 3-6, 9-12).…”

Section: Discussionmentioning

confidence: 99%

“…Jiao et al found a higher rate of detected cancer cells in the bone marrow obtained from rib segment resection than iliac crest aspirate (12). Other authors such as Cote et al used immunohistochemical techniques to detect malignant cells in the bone marrow in 17 out of 43 patients with early stage cancer that had no clinical manifestations of disseminated malignant disease (5). They used in their study two monoclonal cytokeratinspecific antibodies AE-1 and CAM 5.2.…”

Section: Discussionmentioning

confidence: 99%

“…In the early stages of lung cancer, the concentration of tumour cells in the bone marrow is low and their detection by routine imaging techniques, biochemical tests, and microscopic examination is difficult or impossible. Therefore, more advanced techniques such as immunohistochemical and molecular methods are presently used to detect malignant cells in the medulla (5,10,14). Several different antibodies can be used to detect metastases in the bone marrow or lymph nodes.…”

mentioning

confidence: 99%

“…However, they can be useful for the detection of epithelial cells in the bone marrow or lymph nodes where epithelial elements are normally not present. The reported sensitivity of immunohistochemical methods range from one cell in 10 5 to 2-5 in 10 6 normal hematopoetic cells (5,10,14). The objective of the study was to evaluate the usefulness of microscopic examination and immunohistochemical methods for the detection of micrometastases or cancer cells in the bone marrow of patients operated on for nonsmall cell lung cancer (NSCLC), as well as to assess long-term survival and disease free intervals dependent on the presence of cancer metastases in the bone marrow detected by immunohistochemical methods.…”

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confidence: 99%

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The Influence of Immunohistochemical Factors of Bone Marrow Micrometastases on Lung Cancer Patient Survival Rate After Surgical Treatment

Dancewicz

Kowalewski

Bella

et al. 2007

Polish Journal of Surgery

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The detection of micrometastases in patients with operable non-small cell lung carcinoma (NSCLC) could have a considerable influence on the choice of a proper treatment. The aim of the study was to evaluate the usefulness of microscopic examination and immunohistochemistry for the detection of micrometastases or single malignant cells in the bone marrow of patients undergoing surgery for NSCLC, as their late survival and recurrence-free time is dependent on immunohistochemical markers of cancer metastases in the bone marrow. Material and methods. Thirty-five patients were included in the study. Their age range was from 47 to 78 years old. Bone marrow was obtained from a rib during surgery for lung cancer. Both a resected tumour and bone marrow sample were tested for the presence of cytokeratins AE1/AE3, CAM 5.2, CK-7, and CK-18 and other indicators such as CD31 and CD34. The mean time of observation was 871.6 days. Results. Microscopic examination detected no malignant cells or micrometastases in the bone marrow in the analyzed group. Cytokeratin CAM 5.2 was detected in 33 cases (94.23%) in a lung tumour and in 21 cases (60%) in the bone marrow. Statistical analysis (chi 2 NW), showed a statistically significant relationship between the presence of CAM 5.2 expression in a tumour and in the bone marrow. In all analysed cases, the expression of cytokeratin AE1/AE2 was found in a tumour, but was not detected in any bone marrow sample. Cytokeratin CK-7 and CK-18 were present in a tumour in 20 (57.14%) and 23 (65.71%) patients, respectively. In the bone marrow, the expression of cytokeratin CK-7 was found in one case (2.86%), and CK-18 was not found in any patients. Thirteen (37.14%) patients died during followup. Local recurrence was diagnosed in three patients (8.57%) and distant metastases in 15 patients (42.86%). Mean recurrence-free time was 687.7 days. Conclusions. On the basis of immunohistological tests, it was shown that a significant correlation existed between the presence of cytokeratin CAM 5.2 expression in a tumour and in the bone marrow. Its presence in the bone marrow was a good predictive factor for recurrence-free time. Mortality and the frequency of locoregional recurrence and distant metastases depend on pathological lung cancer staging.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Influence of Immunohistochemical Factors of Bone Marrow Micrometastases on Lung Cancer Patient Survival Rate After Surgical Treatment

Dancewicz

Kowalewski

Bella

et al. 2007

Polish Journal of Surgery

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Characterization of disseminated tumor cells

Hosch

Braun

Pantel

2001

Seminars in Surgical Oncology

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The most prominent secondary organs screened for the presence of occult disseminated tumor cells are regional lymph nodes and bone marrow. The current data suggest that micrometastatic cells represent a selected population of dormant cancer cells, which still express a considerable degree of heterogeneity. The analysis of micrometastatic cells will open a new avenue to assess the molecular determinants of both early tumor cell dissemination and subsequent outgrowth into overt metastases. Moreover, identifying therapeutic target structures (e.g., HER2), monitoring the elimination of bone marrow micrometastases, and assessing treatment-resistant tumor cell clones may help in understanding the current limitations of adjuvant systemic therapy. This review summarizes the current knowledge on the biological characteristics of micrometastatic cancer cells in bone marrow and lymph nodes of cancer patients.

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Detection of occult metastasis in patients with breast cancer

Hawes

Neville

Côté

2001

Seminars in Surgical Oncology

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The most important factor affecting the outcome of patients with invasive cancer is whether the tumor has spread, either regionally (to regional lymph nodes) or systemically. However, a proportion of patients with no evidence of systemic dissemination will develop recurrent disease after primary "curative" therapy. Clearly, these patients had occult systemic spread of disease that was undetectable by routinely employed methods (careful pathological, clinical, biochemical, and radiological evaluation). In addition, the success of adjuvant therapy is assumed to stem from its ability to eradicate occult metastases before they become clinically evident. Therefore, methods for the detection of occult metastases in patients with the earliest stage of cancer, i.e., prior to detection of metastases by any other clinical or pathological analysis, have received a great deal of attention.

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Detection of occult metastases in lung carcinomas: Progress and implications for lung cancer staging

Cited by 37 publications

References 42 publications

The Influence of Immunohistochemical Factors of Bone Marrow Micrometastases on Lung Cancer Patient Survival Rate After Surgical Treatment

The Influence of Immunohistochemical Factors of Bone Marrow Micrometastases on Lung Cancer Patient Survival Rate After Surgical Treatment

Characterization of disseminated tumor cells

Detection of occult metastasis in patients with breast cancer

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