title: Mitochondrial DNA genotyping efficiently reveals clonality of synchronous endometrial and ovarian cancers.
abstract: Simultaneous independent primary tumors of the female genital tract occur in 1-2% of gynecological cancer patients, 50-70% of which are synchronous tumors of the endometrium and ovary. Recognition of synchrony upon multiple tumors is crucial for correct prognosis, therapeutic choice, and patient management. Current guidelines for determining synchrony, based on surgical and histopathological findings, are often ambiguous and may require further molecular analyses. However, because of the uniqueness of each tumor and of its intrinsic heterogeneity, these analyses may sometimes be inconclusive. A role for mitochondrial DNA genotyping was previously demonstrated in the diagnosis of synchronous endometrial and ovarian carcinoma. We have analyzed 11 sample pairs of simultaneously revealed endometrial and ovarian cancers and have thereby applied conventional histopathological criteria, current molecular analyses (microsatellite instability, β-catenin immunohistochemical staining/CTNNB1 mutation screening), and mitochondrial DNA sequencing to distinguish separate independent tumors from metastases, comparing the performance and the informative potential of such methods. We have demonstrated that in ambiguous interpretations where histopathological criteria and canonical molecular methods fail to be conclusive, mitochondrial DNA analysis may act as a needle of balance and allow to formulate a diagnosis in 45.5% of our cases. Additional advantages of mitochondrial DNA genotyping, besides the high level of information we demonstrated here, are the easy implementation and the need for small amounts of starting material. Our results show that mitochondrial DNA genotyping may provide a substantial contribution to indisputably recognize the metastatic nature of simultaneously detected endometrial and ovarian cancers and may change the final staging and clinical management of these patients.
authors.affiliation: Department of Medical and Surgical Sciences, Unit of Medical Genetics, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Guerra
authors.affiliation: Department of Medical and Surgical Sciences, Unit of Medical Genetics, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Girolimetti
authors.affiliation: Department of Obstetrics and Gynecology, Oncologic Gynecology Unit, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Anna Myriam
authors.initials: AM
authors.lastname: Perrone
authors.affiliation: Department of Obstetrics and Gynecology, Oncologic Gynecology Unit, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Procaccini
authors.affiliation: Department of Medical and Surgical Sciences, Unit of Medical Genetics, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Kurelac
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceccarelli
authors.affiliation: Laboratory of Molecular Pathology, Anatomic Pathology, Bellaria Hospital, Bologna, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: De Biase
authors.affiliation: Unit of Oncology and Transplant Pathology, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Caprara
authors.affiliation: Institute of Oncology, Medical Oncology Unit, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Zamagni
authors.affiliation: Department of Obstetrics and Gynecology, Oncologic Gynecology Unit, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Pierandrea
authors.initials: P
authors.lastname: De Iaco
authors.affiliation: Department of Pathology, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Santini
authors.affiliation: Department of Medical and Surgical Sciences, Unit of Medical Genetics, University Hospital S.Orsola-Malpighi, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gasparre
mesh_terms: D000328:Adult; D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D003937:Diagnosis, Differential; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial