Predicting Clinical Outcome in Patients Diagnosed with Synchronous Ovarian and Endometrial Cancer

Abstract

Purpose: Patients with synchronous ovarian and endometrial cancers may represent cases of a single primary tumor with metastasis (SPM) or dual primary tumors (DP).The diagnosis given will influence the patient's treatment and prognosis. Currently, a diagnosis of SPM or DP is made using histologic criteria, which are frequently unable to make a definitive diagnosis. Experimental Design: In this study, we used genetic profiling to make a genetic diagnosis of SPM or DP in 90 patients with synchronous ovarian/endometrial cancers.We compared genetic diagnoses in these patients with the original histologic diagnoses and evaluated the clinical outcome in this series of patients based on their diagnoses. Results: Combining genetic and histologic approaches, we were able make a diagnosis in 88 of 90 cases, whereas histology alone was able to make a diagnosis in only 64 cases. Patients diagnosed with SPM had a significantly worse survival than patients with DP (P = 0.002). Patients in which both tumors were of endometrioid histology survived longer than patients of other histologic subtypes (P = 0.025), and patients diagnosed with SPM had a worse survival if the mode of spread was from ovary to endometrium rather than from endometrium to ovary (P = 0.019). Conclusions: Genetic analysis may represent a powerful tool for use in clinical practice for distinguishing between SPM and DP in patients with synchronous ovarian/endometrial cancer and predicting disease outcome. The data also suggest a hitherto uncharacterized level of heterogeneity in these cases, which, if accurately defined, could lead to improved treatment and survival.

The clonal evolution of metastases from primary serous epithelial ovarian cancers

“…As with linkage analysis for tracking inherited transmission in families, the ability to distinguish between different allelic events at the same marker is a very powerful tool for studying clonality. 6,15 In conclusion, we have used genetic analysis of primary ovarian tumors and their associated metastatic lesions from several patients, to evaluate the mechanisms of clonal evolution and metastatic progression. Our data suggest that most, if not all metastases are clonally related to the primary tumors.…”

“…We have found previously that there is no correlation between variation in the pattern of LOH and the size of the PCR product. 4,15 The heterozygosity of these markers ranged from 0.71 to 0.90. Markers that failed PCR amplification in tumor samples were excluded from the analysis.…”

“…We performed additional genotyping in this and a previous study 15 to ensure quality control in scoring LOH data. In a study of 90 ovarian tumors for 22 microsatellite markers, we found 98.1% concordance on repeat DNA extraction/PCR/LOH analyses of the samples; 1,444 of 1,472 informative pairs of samples produced the same result.…”

Synchronous Cancers of the Ovary and Endometrium

“…Eifel et al found that patients with endometrioid cancers at both sites had a better overall prognosis when compared to patients with stage II ovarian disease or stage III endometrial cancer. The GOG study by Ramus et al found that 74 patients with simultaneously detected endometrial and ovarian cancers had an overall good prognosis with a 5-year survival of 85.9 % and 10-year survival of 80.3 % [ 15 ]. Although almost one-third had metastases at operation, only 15 % of the entire study population suffered a recurrence within 5 years of diagnosis.…”

“…MSI is caused by an underlying defect in the mismatch repair (MMR) system. In a study of 90 cases of simultaneous endometrial and ovarian cancers, it was found that histology alone provided a diagnosis in only 61 % of cases, whereas the combination of histology and molecular diagnosis based on LOH at 22 loci and MSI was able to categorize 98 % of cases [ 15 ].…”