Abstract
114 biopsy specimens from 70 patients with ovarian carcinoma at all stages of disease were submitted for assessment of clonogenic capacity in agar. A highly significant correlation was found between agar clonogenicity and patient survival after biopsy. However, problems related to inherent tumour heterogeneity, quality of sample and tissue disaggregation indicate that this technique may have limited applicability in the routine assessment of patients. Only 41 biopsy specimens (36%) from 31 patients (44.3%) complied with the prerequisite criteria for agar clonogenic assessment, namely: (a) the confirmed presence of malignant cells in the biopsy, (b) the ability to prepare a single-cell suspension, and (c) adequate viable cell numbers for assay. Furthermore, although the dominant patterns of agar clonogenic growth could be identified and correlated with stage of disease, the heterogeneity in both initial clonogenic capacity and "self-renewal" capacity assessed by the ability of primary clones to propagate in liquid culture and reclone in agar was too inconsistent for the assay to be used as a prognostic index for the individual patient.
Highlights
In applying the assay to primary human tumour biopsy specimens much greater variability might be encountered; in the light of the known heterogeneity of tumours (Mihich et al, 1979) the specimen may not be representative of the tumour as a whole, and the extremely slow doubling time of many tumours (Tubiana & Malaise, 1976) may enable expression of clonogenic capacity by only that sub-population of stem cells which is capable of the 5-6 doublings required to form a colony within the 21 days of the assay
This paper describes the correlation of growth in agar culture with basic clinical data and discusses the limitations of the agar-culture assay for the assessment of human tumour stem cells in the light of this study
The quality and heterogeneity of biopsy specimens was a major obstacle to the routine application of the clonal agar assay to the assessment of the clonogenic capacity of ovarian tumours
Summary
From the Biological Research Unit and the tGynaecology Unit of the Cancer Institute, 481 Little Lonsdale Street, the *Gynaecological Oncology Unit, Queen Victoria Medical Center; the Gynaecology Department, Royal Melbourne Hospital and the §Professorial Unit and Oncology Unit of the Royal Women's Hospital, Melbourne, Victoria, Australia, 3000. In applying the assay to primary human tumour biopsy specimens much greater variability might be encountered; in the light of the known heterogeneity of tumours (Mihich et al, 1979) the specimen may not be representative of the tumour as a whole, and the extremely slow doubling time of many tumours (Tubiana & Malaise, 1976) may enable expression of clonogenic capacity by only that sub-population of stem cells which is capable of the 5-6 doublings required to form a colony within the 21 days of the assay Such possibilities have significant bearing on the interpretation of assay results. This paper describes the correlation of growth in agar culture with basic clinical data and discusses the limitations of the agar-culture assay for the assessment of human tumour stem cells in the light of this study
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
