Disseminated tumor cells in lymph nodes as a determinant for survival in surgically resected non-small-cell lung cancer.
OBJECTIVE
In recent years, the detection of even a few tumor cells in lymph nodes of patients with surgically resected non-small-cell lung cancer (NSCLC) became possible with immunohistochemical staining procedures. Tumor cells in lymph nodes have been shown to be associated with an increased rate of early recurrence. However, the prognostic significance of this minimal tumor cell spread for overall survival remains unclear.


METHODS
We used the epithelium-specific monoclonal antibody Ber-EP4, which recognizes the 17-1A antigen (also called EGP40 or Ep-CAM), to discover small tumor cell deposits (< or = three cells) in 565 regional lymph nodes judged as tumor-free by conventional histopathology in patients with NSCLC staged as pT1-4, pN0-2, M0, R0. In a prospective analysis, we studied the influence of the detected tumor cells on the cancer recurrence rate and survival of 117 patients.


RESULTS
Ber-EP4-positive cells were found in 27 of 125 patients (21.6%). After an observation period of 64 months, patients with disseminated tumor cells had reduced disease-free survival (P < .0001) and overall survival (P = .0001) rates in univariate analyses (logrank test). Multivariate analysis (Cox model) showed a 2.7 times increased risk for tumor relapse and a 2.5 times increased risk for shorter survival in patients with disseminated tumor cells compared with patients without such cells. Patients without any evidence of histopathologic and immunohistochemical lymph node involvement had an overall survival rate of 78%.


CONCLUSIONS
The immunohistochemical detection of disseminated tumor cells in lymph nodes of patients with completely resected NSCLC is an independent prognostic factor for overall survival.
Kubuschok
B
B
Department of Thoracic Surgery, Central Hospital Gauting, Germany.
Passlick
B
B
Izbicki
J R
JR
Thetter
O
O
Pantel
K
K
D000951:Antigens, Neoplasm / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015815:Cell Adhesion Molecules / Q000032:analysis; D018572:Disease-Free Survival; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009360:Neoplastic Cells, Circulating / Q000276:immunology / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule