Assessment of differentiation in adenocarcinoma cells from pleural effusion by peripheral airway cell markers and their diagnostic values

Ultrastructural studies have shown that Clara cell-type is a more common type of adenocarcinoma than alveolar type II cell-type, and that both types may provide better prognosis than other types, indicating an importance of differentiation toward peripheral airway cells. Pulmonary surfactant protein (SP)-A is a specific marker for both alveolar type II cells and Clara cells in peripheral lung tissues, while SP-C and Clara cell 10 kD protein (CC10) may be particularly and highly specific to alveolar type II cells and Clara cells, respectively. The aims of this study were to assess the differentiation of adenocarcinoma cells in pleural effusions by evaluating the expression of these cell markers and to evaluate their values as diagnostic tools for judging the cause of pleural effusion. We examined pleural effusions from 52 patients; 20 with primary lung adenocarcinomas, 6 with small cell lung carcinomas, 11 with metastatic malignant tumors and 15 with non-neoplastic diseases. The cell pellets from effusions were subjected to immunocytochemical staining for SP-A, proSP-C, a precursor of SP-C, and CC10. By this immunocytochemical study for SP-A and proSP-C, 10 (50%) and 6 (30%) of 20 adenocarcinomas, respectively, showed a positive immunoreactivity in their effusion cells, while none of them expressed CC10. Alveolar type II cells therefore may be the main progenitor cells of some adenocarcinomas. In pleural effusions from patients with primary lung adenocarcinomas, reverse transcriptase-polymerase chain reaction (RT-PCR) for SP-A mRNA showed a sensitivity of 83%, while, in all remaining patients, these assays were negative. In conclusion, we demonstrated that lung adenocarcinomas, which are partially differentiated toward alveolar type II cells, are not as rare as previously thought, and that both the RT-PCR and immunocytochemical analyses for SP-A and pro-SP-C could be worthy indicators of differential diagnosis.