Molecular analysis of an immature ovarian teratoma with gliomatosis peritonei and recurrence suggests genetic independence of multiple tumors

Abstract

Immature ovarian teratoma is a common germ cell tumor of young women. Patients with immature teratoma often exhibit multiple neoplasms, including tumors outside the ovaries, and occasionally a rare benign condition termed gliomatosis peritonei (GP). These multiple neoplasms are generally believed genetically-linked progeny of the ovarian tumor resulting from local recurrence/spread. In this study, we performed a molecular analysis of a single patient clinically diagnosed with immature ovarian teratoma, GP, and recurrent pelvic mucinous teratoma. Microsatellite PCR and amplicon analysis was performed to genetically characterize tissue samples from omental glial implants and multiple peritoneal tumors. PCR-based amplification of microsatellite markers identifies unique genetic differences (allelic variation) between tumors resulting from divergent natural histories among multiple tumor nodules in a single patient. A total of 21 different microsatellite markers were employed, and seven provided informative results (D3S1744, D6S1056, D7S2846, D14S306, D16S764, D18S858, D22S420). These markers demonstrated mutually exclusive genetic differences among the tumors from this patient, establishing the neoplasms as genetically distinct from each other (non-identical), and that no lineage relationship exists among them. This observation suggests that the multiple tumors arising in this patient with immature ovarian teratoma, GP, and recurrent pelvic mucinous neoplasm represent multiple independent tumors rather than true tumor recurrence/spread. The results of this study suggest strongly that patients with recurrent teratoma may be afflicted with a tumor-prone syndrome where one or more peritoneal cell types or populations are predisposed to neoplastic conversion and formation of tumors as a result of an endogenous or exogenous neoplastic stimuli.