FLOW CYTOMETRIC DNA-PLOIDY AND S-PHASE HETEROGENEITY IN ADVANCED OVARIAN-CARCINOMA

Background. The prognostic significance of flow cytometric DNA ploidy and S-phase fraction (SPF) in ovarian cancer has been controversial. I n the current study, the authors analyzed tumor heterogeneity in respe ct to DNA index DI and SPF. Methods. Flow cytometric variation in DI a nd SPF among representative fresh tumor material from the primary tumo r, metastasis, and malignant effusions from the same patient was analy zed. Results. One hundred thirty-two samples from 47 patients were ana lyzed, and 119 samples from 42 patients were evaluable. Stable DI betw een different samples was found in 34 patients, whereas heterogeneity was found in 8 patients (19%). The metastases showed stable DNA conten t. The malignant effusion samples often lacked tumor cells. The repres entative ones were often DNA diploid. In 21% of the aneuploid samples, the SPF could not be analyzed. In 38% of the aneuploid samples, the s tem line constituted less than 15% of measured nuclei. In these sample s, a negative correlation between SPF and percentage of aneuploid cell s was found, making SPF unreliable. Correct SPF measurement was thus p ossible in only 41% of the aneuploid samples, and in these tumors, SPF values varied considerably among different samples from the same pati ent, illustrated by a median SPF difference of 11% (range, 0-28%). Con clusions. Tumor DI heterogeneity existed in 19% of tumors. SPF depende d on the amount of aneuploid cells in case of small stem lines and var ied considerably, making its use as a prognostic factor doubtful. To e nsure that all tumor stem lines are represented, at least two biopsy s pecimens from any solid tumor should be analyzed.