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The clonal assay of head and neck tumor cells: Results and clinical correlations
Author(s) -
Johns Michael E.
Publication year - 1982
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1288/00005537-198207001-00001
Subject(s) - collagenase , biology , in vitro , cloning (programming) , cell culture , cancer research , pathology , enzyme , medicine , genetics , biochemistry , computer science , programming language
Since the application of in vitro techniques to assess the activity of antibiotics against bacteria, there has been an interest in using tissue culture techniques to predict the effects of antineoplastic agents on human cancers. Generally, the in vitro effects have not always correlated with the clinical actions. Recently a refined method for measuring the number of cells in a given tumor capable of being cloned and the effects of cytotoxic agents on the cloned tumor cell growth has been developed. There is now good clinical correlation in patients with multiple myeloma and ovarian carcinomas with the responses to chemotherapeutic agents determined in vitro. The soft agar clonal assay has been used to study the biology of head and neck tumor stem cells. At the University of Virginia, 73 squamous cell carcinomas (SCC) of the head and neck were cloned. The basic characteristics of cloned head and neck tumor cell growth was studied in terms of 1 . single cell origin, 2 . cloning efficiency, 3 . colony development, 4 . linearity, 5 . effects of enzyme disaggregation and 6 . ultrastructural characteristics. The clinical characteristics of T class, N class, stage, survival, and Jakobsson's rating of tumor differentiation were correlated with cloning efficiency to determine if there are predictive survival data. Obtaining single cells from the tumors continues to be a major problem. The use of enzymes (collagenase and DNase) has aided in the production of single cells for culture. The enzymes are superior to mechanical techniques and do not compromise viability or cloning efficiency. Electron microscopy is valuable in documenting the malignant nature of the cloned tumor cells. Of the 73 squamous cell carcinomas that were cultured, 49% demonstrated clonal growth. A number of non‐squamous cell carcinomas were also successfully cloned. The cloning efficiency was variable ranging from .001% to .05%. For the SCC's the median cloning efficiency was .005%. Twenty‐nine SCC's were available for clinical correlations. Chemosensitivity testing was often not feasible because of inadequate numbers of tumor cells in the small specimens and frequent failure of clonal growth. A statistically significant correlation of high cloning efficiency with advanced nodal class, stage, and survival was observed. There was no correlation with T class or Jakobsson's rating. A cloning efficiency of ≤ .005% was associated with a high likelihood of death from disease or the development of recurrent disease. For head and neck squamous cell carcinomas, the determination of cloning efficiency in soft agar appears to be a valuable prognostic indicator.