FREQUENCY AND DISTRIBUTION OF OCCULT MICROMETASTASES IN LYMPH-NODES OF PATIENTS WITH NON-SMALL-CELL LUNG-CARCINOMA

Background: Accurate assessment of the presence and absence of tumor in the regional lymph nodes is critical in assessment of prognosis for patients with lung cancer. Development of sensitive immunohistochemical techniques and specific monoclonal antibodies has increased our capacity, in melanoma and breast cancer, to detect small groups of tumor cells or even single tumor cells in lymph nodes that appear to be tumor free in conventionally stained sections. Purpose: This retrospective study was designed to assess whether use of a polyclonal antikeratin reagent in immunohistochemical analysis offers any advantage over conventional histopathology in detection of regional lymph node metastases in non-small-cell lung cancer. Methods: Paraffin-embedded tissue sections from regional lymph nodes of 65 patients with non-small-cell lung cancer were studied. We examined tissue from 588 nodes of 60 patients with a diagnosis of disease confined to the lung and from 72 nodes of five patients with a diagnosis of metastasis to some nodes. A polyclonal antikeratin antibody was applied to the lymph node tissue sections, using the avidin-biotin complex immunoperoxidase technique. Results: Single tumor cells and small clusters of tumor cells (occult micrometastases) not visible on routine evaluation were readily detected in 38 (63%) of the 60 patients whose nodes appeared to be negative on examination of hematoxylin-eosin-stained slides. In the five patients with a diagnosis of node-positive non-small-cell lung cancer, rive (10%) of 51 nodes that were tumor free on conventional examination contained metastases. Metastatic tumor cells were most often located in the subcapsular or medullary sinuses. The lymph nodes that contained occult tumor cells were those located nearest to the tumor, mainly in peribronchial and hilar locations. The median survival of patients with occult metastases (1977 days) was shorter than that of patients whose nodes contained no tumor (2456 days) but was longer than that of patients whose nodes contained metastases detectable on hematoxylin-eosin-stained slides (927 days). Conclusions: Our results suggest that, in patients with non-small-cell lung cancer, metastatic involvement of regional lymph nodes is more frequent than was previously determined by the conventional histologic method and substantially more frequent than in other tumor types, such as melanoma and breast cancer. Implications: The high frequency of occult nodal metastases in non-small-cell lung cancer makes it clear that, without immunohistochemistry, disease is understaged in many patients. Therefore, it seems essential that immunohistochemical evaluation of the lymph nodes be undertaken in clinical trials.