Lymph Node Micrometastases in Lung Cancer
Lung cancer remains the most common cause of cancer-related death in Europe and the United States (9, 10). Nonsmall-cell lung cancer (NSCLC) affects approximately 80% of all lung cancer patients (5, 9). Surgery remains the gold standard treatment for locoregional NSCLC, and pathological lymph node (pN) status has remained the strongest clinical prognostic characteristic in early stages of operable NSCLC (21, 23). However, even in early stages, the 5-year survival rate of N0 patients remains at only 60–70% after complete resection of the primary tumor (7, 17). This suggests that tumor cell dissemination occurs early and occult micrometastases or single disseminated tumor cells (DTC), which are not discovered by conventional histopathologic methods, may be present in the lymph nodes at the time of surgery (6, 16, 18, 22, 26). Detection of these cells might potentially improve clinical lymph node staging and help to identify patients who could benefit from adjuvant or neoadjuvant therapy.
KeywordsNSCLC Patient Disseminate Tumor Cell Quantitative Reverse Transcriptase Polymerase Chain Reaction Tumor Cell Dissemination CK19 mRNA
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- 3.D’Cunha J, Corfits AL, Herndon JE 2nd, Kern JA, Kohman LJ, Patterson GA, Kratzke RA, Maddaus MA (2002) Molecular staging of lung cancer: Real-time polymerase chain reaction estimation of lymph node micrometastatic tumor cell burden in stage I nonsmall cell lung cancer–preliminary results of Cancer and Leukemia Group B Trial 9761. J Thorac Cardiovasc Surg 123: 484–491; discussion 491, 2002.Google Scholar
- 5.el-Torky M, el-Zeky F, Hall JC (1990) Significant changes in the distribution of histologic types of lung cancer. A review of 4928 cases. Cancer 65: 2361–2367.Google Scholar
- 10.Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics, 2005. CA Cancer J Clin 55:10–30, 2005.Google Scholar
- 11.Kraemling M, Ruosaari S, Ylstra B, Pantel K, Wikman H (2006) Genomic profiles associated with early micrometastatic spread in lung cancer. AACR abstract, AACR #1830.Google Scholar
- 13.Kufer P, Zippelius A, Lutterbuse R, Mecklenburg I, Enzmann T, Montag A, Weckermann D, Passlick B, Prang N, Reichardt P, Dugas M, Kollermann MW, Pantel K, Riethmuller G (2002) Heterogeneous e pression of MAGE-A genes in occult disseminated tumor cells: a novel multimarker reverse transcription-polymerase chain reaction for diagnosis of micrometastatic disease. Cancer Res 1;62(1):251–61.Google Scholar
- 15.Le Pimpec-Barthes F, Danel C, Lacave R, Ricci S, Bry X, Lancelin F, Leber C, Milleron B, Fleury-Feith J, Riquet M, Bernaudin JF (2005) Association of CK19 mRNA detection of occult cancer cells in mediastinal lymph nodes in non-small cell lung carcinoma and high risk of early recurrence. Eur J Cancer 41:306–312.PubMedCrossRefGoogle Scholar
- 16.Maeda J, Inoue M, Okumura M, Ohta M, Minami M, Shiono H, Shintani Y, Matsuda H, Matsuura N (2006) Detection of occult tumor cells in lymph nodes from non-small cell lung cancer patients using reverse transcription-polymerase chain reaction for carcinoembryonic antigen mRNA with the evaluation of its sensitivity. Lung Cancer 52(2):235–40.PubMedCrossRefGoogle Scholar
- 27.Pantel and Panabières (2006) aceepted by Nature Clinical Practice Oncology.Google Scholar
- 30.Putz E, Witter K, Offner S, Stosiek P, Zippelius A, Johnson J, Zahn R, Riethmuller G, Pantel K (1999) Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res 59(1):241–8.PubMedGoogle Scholar
- 35.Wang XT, Sienel W, Eggeling S, Ludwig C, Stoelben E, Mueller J, Klein CA, Passlick B (2005) Detection of disseminated tumor cells in mediastinoscopic lymph node biopsies and lymphadenectomy specimens of patients with NSCLC by quantitative RT-PCR. Eur J Cardiothorac Surg 28:26–32.PubMedCrossRefGoogle Scholar
- 38.Yasumoto K, Osaki T, Watanabe Y, Kato H, Yoshimura T (2003) Prognostic value of cytokeratin-positive cells in the bone marrow and lymph nodes of patients with resected nonsmall cell lung cancer: a multicenter prospective study. Ann Thorac Surg 76(1):194–201; discussion 202.Google Scholar