Flow cytometric DNA ploidy and S-phase heterogeneity in advanced ovarian carcinoma

Abstract

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.