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. In the current study, the authors analyzed tumor heterogeneity in respect to DNA index DI and SPF. Methods. Flow cytometric variation in DI and SPF among representative fresh tumor material from the primary tumor, metastasis, and malignant effusions from the same patient was analyzed. Results. One hundred thirty-two samples from 47 patients were analyzed, and 119 samples from 42 patients were evaluable. Stable DI between different samples was found in 34 patients, whereas heterogeneity was found in 8 patients (19%). The metastases showed stable DNA content. The malignant effusion samples often lacked tumor cells. The representative ones were often DNA diploid. In 21% of the aneuploid samples, the SPF could not be analyzed. In 38% of the aneuploid samples, the stem line constituted less than 15% of measured nuclei. In these samples, a negative correlation between SPF and percentage of aneuploid cells was found, making SPF unreliable. Correct SPF measurement was thus possible in only 41% of the aneuploid samples, and in these tumors, SPF values varied considerably among different samples from the same patient, illustrated by a median SPF difference of 11% (range, 0-28%). Conclusions. Tumor DI heterogeneity existed in 19% of tumors. SPF depended on the amount of aneuploid cells in case of small stem lines and varied considerably, making its use as a prognostic factor doubtful. To ensure that all tumor stem lines are represented, at least two biopsy specimens from any solid tumor should be analyzed. Cancer 1994; 73:1870-7. Key words: ovarian carcinoma, tumor heterogeneity, DNA ploidy, S-phase fraction.