Nuclear polymorphism in osteosarcomas as a prognostic factor for the effect of chemotherapy. A quantitative study

A current strategy for osteosarcoma treatment is neo-adjuvant chemotherapy prior to the resection of the tumour. It appears that some tumours respond very well to the cytostatic therapy, while others show little or no effect. It is desirable to be able predict the response of the tumour before starting chemotherapy. 16 biopsy specimens from patients with osteosarcoma who had been treated according to the protocol of the study COSS-80 and COSS-82 were examined. 100 tumour cells from each biopsy have been measured by an electronic interactive image analysis system (IBAS II; Kontron/ZEISS). After completion of chemotherapy en bloc resection of the tumour was performed. The entire surgical specimen was completely examined at two levels by means of undecalcified sections, and assigned a grade for the effect of chemotherapy analogous to the grading of Salzer-Kuntschik et al. (1983). The quantitative analysis of tumour cell nuclei revealed two different patterns of nuclear sizes, which were correlated significantly with the chemotherapy response (P less than 0.002). Tumour cell nuclei of well responders were significantly larger and showed a greater variance in size (mean value 66 + 41 micron 2), than those of poor responders (mean value 38 + 18 micron 2). We conclude from our results that quantitative analysis and classification of nuclear size of osteosarcoma cells may be useful for predicting chemotherapy response in patients with osteosarcoma.