Analysis of tumor heterogeneity in a patient with synchronously occurring female genital tract malignancies by DNA flow cytometry, DNA fingerprinting, and immunohistochemistry

Abstract

A case of a patient with bilateral ovarian cancer and a uterine malignant mesodermal mixed tumor with ascites and metastatic disease is presented. Flow cytometry, DNA fingerprinting, and immunohistochemistry were performed to assess the origin of these malignancies. Ploidy analysis showed that both ovarian tumors had different aneuploid stemlines (DNA index [DI] = 1.64, 1.85, right ovary and DI = 1.73, left ovary) indicating independent origins. One of the stemlines in the right ovary (DI = 1.64) was also present in the ascites cells, whereas omentum metastases showed the same stemline (DI = 1.73) as the left ovarian tumor. The uterine malignancy contained three aneuploid stemlines. The highest stemline was associated with epithelial differentiation, but a metastatic origin from the left ovarian tumor seems unlikely. DNA fingerprinting analysis revealed a common change in restriction fragment length pattern in the DNA from all tumor localizations as compared with the patient's constitutional DNA. These results indicate that DNA flow cytometry can be helpful in discriminating intragenital metastatic disease from multiple primary tumors.