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Positive Correlation between Histological Tumor Involvement and Generationof Tumor Cell ColOniesin Agarose in SpecimensTaken Directly from Patients with Small-Cell Carcinoma of the Lung

Twenty-seven specimens for in vitro agarose clonogenicity testing were obtained from 25 patients with small-cell carci noma of the lung (SCCL). The specimens were obtained from bone marrows, pleural effusions, lymph nodes, and liver biop sies. Colony formation was seen in 14 of 15 specimens that were histologically involved with SCCL, but no colony growth was seen in the 12 patient specimens without histocytopath ological evidence of SCCL, including seven bone marrow spec imens. Cytological examination of the agarose colonies con firmed their SCCL origin. Colonies reached sizes of 50 to 1000 cells in 7 to 10 days, indicating an in vitro doubling time of less than 24 hr, remarkably shorter than the population doubling times measured in patients. None of the 100 clones picked from these specimens demonstrated the ability to continuously replicate in vitro. These results show an excellent correlation between agarose colony formation and histological tumor in volvement and a more rapid in vitro doubling time than that seen in vivo and demonstrate that standard tissue culture conditions do not allow demonstration of a self-renewing stem cell in fresh tumor specimens of SCCL.