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

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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.

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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.

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Authors and Affiliations

  1. 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

    Laura Ardighieri, Sara Conzadori, Mattia Bugatti, Marcella Falchetti, Carla Maria Donzelli & Fabio Facchetti

  2. Department of Clinical and Experimental Science, University of Brescia, Spedali Civili di Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy

    Luigi Mori

  3. “Angelo Nocivelli” Institute of Molecular Medicine, Division of Gynecologic Oncology, University of Brescia, Brescia, Italy

    Antonella Ravaggi

  4. Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy

    Franco E. Odicino

Authors
  1. Laura Ardighieri
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  2. Luigi Mori
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  3. Sara Conzadori
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  4. Mattia Bugatti
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  6. Carla Maria Donzelli
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  7. Antonella Ravaggi
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  8. Franco E. Odicino
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  9. Fabio Facchetti
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Correspondence to Laura Ardighieri.

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Ardighieri, L., Mori, L., Conzadori, S. et al. Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship. Virchows Arch 469, 61–69 (2016). https://doi.org/10.1007/s00428-016-1933-x

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  • DOI: https://doi.org/10.1007/s00428-016-1933-x

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