POSITIVE CORRELATION BETWEEN HISTOLOGICAL TUMOR INVOLVEMENT AND GENERATION OF TUMOR-CELL COLONIES IN AGAROSE IN SPECIMENS TAKEN DIRECTLY FROM PATIENTS WITH SMALL-CELL CARCINOMA OF THE LUNG

Abstract

Twenty-seven specimens for in vitro agarose clonogenicity testing were obtained from 25 patients with small-cell carcinoma of the lung (SCCL). The specimens were obtained from bone marrows, pleural effusions, lymph nodes and liver biopsies. 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 histocytopathological evidence of SCCL, including 7 bone marrow specimens. Cytological examination of the agarose colonies confirmed their SCCL origin. Colonies reached sizes of 50-1000 cells in 7-10 days, indicating an in vitro doubling time of < 24 h, 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. An excellent correlation between agarose colony formation and histological tumor involvement was shown and standard tissue culture conditions apparently do not allow demonstration of a self-renewing stem cell in fresh tumor specimens of SCCL.