Abstract
The proliferative potential of human solid tumours, in vivo, was investigated using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry (FCM). Patients with solid tumours from a variety of sites were injected with 500 mg BrdUrd, intravenously, several hours prior to biopsy or surgical excision. The labelling index (LI), duration of S-phase (Ts) and thus the potential doubling time (Tpot) could be measured within 24 h of sampling. The results show that both the LI and Ts vary greatly between tumours (Ts ranges from 5.8 to 30.7 h). However, within this study of 26 evaluable patients, tumours of the same tissue origin tended to have similar Ts values. Melanomas had the shortest Ts (8.8 h), nine patients with head and neck cancer had Ts values ranging from 5.8 to 18.8 h (median 12.5 h). The longest Ts values (24 h) were found in lung and rectum. The estimates of Tpot ranged from only 3.2 days in an oat cell carcinoma to 23.2 days in a lymphoma. The striking feature of the study was that 38% of the tumours had a potential doubling time of 5 days or less. We found no relationship between proliferation and histopathological differentiation or DNA ploidy. It should now be possible to assess the prognostic significance of pretreatment cell kinetic measurements which may, in the future, aid in the selection of treatment schedules for the individual patient.
Highlights
The cellular proliferation of human cancer has been the subject of much study over the years, aimed at rationalising treatment so that schedules more suited to the cell kinetic characteristics of individual tumours can be given
The result is not achieved in a time-scale suitable for the clinician to use if treatment is to be based on cell kinetic characteristics
We have previously shown that it is possible to measure the labelling index (LI) of human tumours following an in vivo injection of BrdUrd, and using mouse tumours have shown that the BrdUrd technique gives the same information as the use of 3HTdR (Wilson et al, 1985)
Summary
The cellular proliferation of human cancer has been the subject of much study over the years, aimed at rationalising treatment so that schedules more suited to the cell kinetic characteristics of individual tumours can be given. Progress has been hampered by the nature of the techniques available to measure cell kinetic parameters. The incidence of mitotic figures has been used to relate cell production rate to histological parameters and patient survival (Weiss, 1971). This parameter has failed to demonstrate any significant correlation with survival. The result is not achieved in a time-scale suitable for the clinician to use if treatment is to be based on cell kinetic characteristics. Its wide use in vivo is precluded due to ethical considerations involved in administering a radioactive precursor of DNA and the requirement for multiple biopsies if cell cycle measurements are to be made
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