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Virchows Archiv

, Volume 469, Issue 1, pp 61–69 | Cite as

Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship

  • Laura ArdighieriEmail author
  • Luigi Mori
  • Sara Conzadori
  • Mattia Bugatti
  • Marcella Falchetti
  • Carla Maria Donzelli
  • Antonella Ravaggi
  • Franco E. Odicino
  • Fabio Facchetti
Original Article

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.

Keywords

p53 TP53 Carcinosarcoma Bilateral STIC 

Notes

Acknowledgments

LA was supported by Fondazione Beretta (Brescia, Italy). We wish to thank Dr. Domenico Allegra (Fondazione Filarete, Viale Ortles 22, Milano, Italy) for help in laser microdissection and Laura Fappani, Paola Bossini, and Chiara Barisani for technical assistance.

Compliance with ethical standards

Conflict of interest

All the authors have read and approved the final version of the manuscript and declare that there are no conflicts of interest.

Supplementary material

428_2016_1933_MOESM1_ESM.pdf (312 kb)
ESM 1 (PDF 311 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Laura Ardighieri
    • 1
    Email author
  • Luigi Mori
    • 2
  • Sara Conzadori
    • 1
  • Mattia Bugatti
    • 1
  • Marcella Falchetti
    • 1
  • Carla Maria Donzelli
    • 1
  • Antonella Ravaggi
    • 3
  • Franco E. Odicino
    • 4
  • Fabio Facchetti
    • 1
  1. 1.Department of Molecular and Translational Medicine, Section of PathologyUniversity—Spedali Civili of BresciaBresciaItaly
  2. 2.Department of Clinical and Experimental ScienceUniversity of BresciaBresciaItaly
  3. 3.“Angelo Nocivelli” Institute of Molecular Medicine, Division of Gynecologic OncologyUniversity of BresciaBresciaItaly
  4. 4.Department of Obstetrics and GynecologyUniversity of BresciaBresciaItaly

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