Intratumoral dna heterogeneity correlated with lymph node involvement and surgical staging in epithelial ovarian cancer by flow cytometry

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Abstract
Background. Flow cytometry (FCM)-measured DNA content may be a predictor in the prognosis of ovarian cancer. Multiple specimens taken from the same ovarian tumor may show a variation in DNA content (i.e., intra-tumoral DNA heterogeneity). We measured the FCM DNA content of multiple specimens from the same tumor in ovarian cancer, and the relationship among DNA ploidy, intratumoral DNA heterogeneity, retroperitoneal lymph node involvement, and surgical staging was evaluated. Methods. Forty-one patients with primary epithelial ovarian cancer were included in the study. The FCM-measured DNA content of multiple fresh tumor specimens taken from different parts of the same ovarian tumor from each patient was measured. When aneuploidy was observed in at least one specimen from the same tumor, the tumor was defined as an aneuploid tumor. If there were two or more different aneuploid stem lines with a variation of DNA indices (differences of the DNA indices >0.15) from the same tumor, the presence of intratumoral DNA heterogeneity was defined. Results. Diploid tumor was found in 8 (19.5%) of the 41 patients, and aneuploid tumor with intratumoral DNA heterogeneity was found in 20 (48.8%). None of the eight patients with diploid tumors demonstrated lymph node involvement. In contrast, lymph node involvement was found in 14 (70.0%) of 20 patients with intratumoral DNA heterogeneity. There was a significant different incidence of lymph node involvement between the groups with and without intratumoral DNA heterogeneity (P ≤ 0.01). The incidence of intratumoral DNA heterogeneity significantly correlated with the International Federation of Gynecology and Obstetrics staging (P ≤ 0.01), while that of aneuploid tumor did not. Conclusions. Intratumoral DNA heterogeneity reflected a malignant potential for lymph node involvement and its progression in epithelial ovarian cancer. Cancer 1994; 73:3011–4.