Implication of genomic characterization in synchronous endometrial and ovarian cancers of endometrioid histology
Objectives
Synchronous endometrial and
ovarian carcinomas (SEOCs) present gynecologic oncologists with a
challenging diagnostic puzzle:
discriminating between double primary
cancers and single primary cancer with metastasis. We aimed to determine
the clonal relationship between
simultaneously diagnosed endometrial
and ovarian carcinomas.
Methods (Taiwan)
Fourteen
pairs of SEOCs of endometrioid type and two pairs of SEOCs with
disparate histologic types (control for dual primary tumors) were
subjected to massively parallel sequencing (MPS) and molecular inversion
probe microarrays.
Results
Thirteen
of the 14 pairs of SEOCs harbored
somatic mutations shared by both
uterine and ovarian lesions, indicative of clonality. High degree of
chromosomal instability in the tumors from 10 patients who received
adjuvant chemotherapy, of whom 9 had synchronous carcinomas with
significantly overlapping copy number alterations (CNAs),
suggestive of
single primary tumors with metastasis. The
clonal relationship
determined by
genomic analyses did not agree with clinicopathological
criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian
and endometrial carcinomas in 4 patients, who did not receive adjuvant
chemotherapy and experienced no recurrent diseases. In contrast, two of
the 10 patients with chromosomally unstable cancers developed recurrent
tumors.
Conclusion
Our findings
support a
recent paradigm-shifting concept that most SEOCs (
Synchronous endometrial and
ovarian carcinomas) originate
from a single tumor. It also casts
doubt on the clinicopathological
criteria used to distinguish between dual primary tumors and single
primary tumor with metastasis. Testing of CNAs on SEOCs may help
determining the need of adjuvant therapy.
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