title: Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship.
abstract: Pelvic carcinosarcomas (PCSs) are rare aggressive biphasic tumors that localize in the ovary, fallopian tube, or peritoneum and present frequently as bilateral disease. We undertook a morphological, p53 immunohistochemical and TP53 gene mutational analysis study in a single institution cohort of 16 PCSs in order to investigate the nature of bilateral tumors and to shed light on their origin and pathogenesis. Of the 16 patients, 10 presented with bilateral disease, 6 with a carcinosarcoma in both adnexa, and the remaining cases with a carcinosarcoma in one adnexum and a carcinoma in the opposite. The carcinoma component showed high-grade serous features in 13/16 of cases (81 %). In 10 patients (63 %), a serous tubal intraepithelial carcinoma (STIC) was found, in one case bilateral, making a total of 11 STICs. STIC was found only in cases with a carcinoma component with high-grade serous features. All 10 bilateral tumors and all 11 PCS-associated STICs showed a similar p53 immunostaining pattern. At mutation analysis of the TP53 gene, all five bilateral PCS contained an identical mutation in both localizations. Furthermore, a TP53 mutation was found in 8 of 10 STICs, with an identical mutation in the associated PCS. The finding of similar p53 immunostaining in all bilateral cases and identical TP53 mutations in most PCS-associated STIC provides evidence for a clonal relation between these neoplastic lesions, supporting a metastatic nature of bilateral PCS and suggesting that they have an extraovarian origin in a STIC.
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University-Spedali Civili of Brescia, Spedali Civili di Brescia, Unita' Operativa di Anatomia Patologica, Piazzale Spedali Civili 1, 25123, Brescia, Italy. lauraardighieri@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Ardighieri
authors.affiliation: Department of Clinical and Experimental Science, University of Brescia, Spedali Civili di Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Mori
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University-Spedali Civili of Brescia, Spedali Civili di Brescia, Unita' Operativa di Anatomia Patologica, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Conzadori
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University-Spedali Civili of Brescia, Spedali Civili di Brescia, Unita' Operativa di Anatomia Patologica, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bugatti
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University-Spedali Civili of Brescia, Spedali Civili di Brescia, Unita' Operativa di Anatomia Patologica, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Falchetti
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University-Spedali Civili of Brescia, Spedali Civili di Brescia, Unita' Operativa di Anatomia Patologica, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
authors.forename: Carla Maria
authors.initials: CM
authors.lastname: Donzelli
authors.affiliation: "Angelo Nocivelli" Institute of Molecular Medicine, Division of Gynecologic Oncology, University of Brescia, Brescia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Ravaggi
authors.affiliation: Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
authors.forename: Franco E
authors.initials: FE
authors.lastname: Odicino
authors.affiliation: Department of Molecular and Translational Medicine, Section of Pathology, University-Spedali Civili of Brescia, Spedali Civili di Brescia, Unita' Operativa di Anatomia Patologica, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
mesh_terms: D000368:Aged; D002278:Carcinoma in Situ / Q000235:genetics; D002296:Carcinosarcoma / Q000235:genetics / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010386:Pelvic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000473:pathology
keywords: Bilateral; Carcinosarcoma; STIC; TP53; p53