OBJECTIVES: Recent advances in molecular biology and genetics have created new diagnostic and treatment possibilities in clinical oncology. We evaluated the usefulness of molecular biological factors in primary tumor and micrometastasis in the bone marrow and pathological negative (pN0) lymph nodes as prognostic parameters in non-small-cell lung cancer (NSCLC) patients. METHODS: Pathological specimens were collected from 129 NSCLC patients to analyze molecular biological markers, including K-ras, p53, Rb, p16, loss of heterozygosity (LOH) at 3p, vascular endothelial growth factor (VEGF), and telomerase activity. Bone marrow samples from 250 NSCLC patients and pN0 lymph nodes from 85 of these patients were collected for micrometastasis detection by immunohistochemistry against cytokeratin. RESULTS: p53 abnormalities and 3p LOH were significantly associated with reduced patient survival in adenocarcinoma, whereas VEGF expression was significantly associated with reduced survival in a squamous cell carcinoma histological subtype by univariate or multivariate analysis. We identified micrometastatic tumor cells in bone marrow of 78 (31.2%) of 250 patients and in pN0 lymph nodes of 26 (30.6%) of 85 patients. Both bone marrow and lymph nodal micrometastases were associated with decreased survival among patients with stage I, however, only lymph nodal micrometastasis had a significant impact on survival. CONCLUSIONS: Molecular biological features of primary tumor and micrometastatic status appear useful in defining groups of patients with a poor prognosis who could benefit from adjuvant systemic treatment.
OBJECTIVES: Recent advances in molecular biology and genetics have created new diagnostic and treatment possibilities in clinical oncology. We evaluated the usefulness of molecular biological factors in primary tumor and micrometastasis in the bone marrow and pathological negative (pN0) lymph nodes as prognostic parameters in non-small-cell lung cancer (NSCLC) patients. METHODS: Pathological specimens were collected from 129 NSCLCpatients to analyze molecular biological markers, including K-ras, p53, Rb, p16, loss of heterozygosity (LOH) at 3p, vascular endothelial growth factor (VEGF), and telomerase activity. Bone marrow samples from 250 NSCLCpatients and pN0 lymph nodes from 85 of these patients were collected for micrometastasis detection by immunohistochemistry against cytokeratin. RESULTS:p53 abnormalities and 3p LOH were significantly associated with reduced patient survival in adenocarcinoma, whereas VEGF expression was significantly associated with reduced survival in a squamous cell carcinoma histological subtype by univariate or multivariate analysis. We identified micrometastatic tumor cells in bone marrow of 78 (31.2%) of 250 patients and in pN0 lymph nodes of 26 (30.6%) of 85 patients. Both bone marrow and lymph nodal micrometastases were associated with decreased survival among patients with stage I, however, only lymph nodal micrometastasis had a significant impact on survival. CONCLUSIONS: Molecular biological features of primary tumor and micrometastatic status appear useful in defining groups of patients with a poor prognosis who could benefit from adjuvant systemic treatment.
Authors: W Krüger; C Krzizanowski; M Holweg; M Stockschläder; N Kröger; R Jung; K Mross; W Jonat; A R Zander Journal: J Cancer Res Clin Oncol Date: 1996 Impact factor: 4.553
Authors: J L Cordell; B Falini; W N Erber; A K Ghosh; Z Abdulaziz; S MacDonald; K A Pulford; H Stein; D Y Mason Journal: J Histochem Cytochem Date: 1984-02 Impact factor: 2.479
Authors: N W Kim; M A Piatyszek; K R Prowse; C B Harley; M D West; P L Ho; G M Coviello; W E Wright; S L Weinrich; J W Shay Journal: Science Date: 1994-12-23 Impact factor: 47.728
Authors: T Mitsudomi; T Oyama; K Nishida; A Ogami; T Osaki; K Sugio; K Yasumoto; K Sugimachi; A F Gazdar Journal: Clin Cancer Res Date: 1996-07 Impact factor: 12.531