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. 2025 May 5.
doi: 10.1007/s00428-025-04104-7. Online ahead of print.

P-cadherin overexpression is associated with early transformation of the Fallopian tube epithelium and aggressiveness of tubo-ovarian high-grade serous carcinoma

Rita Canário  1   2   3   4 , Ana Sofia Ribeiro  2 , Inês Morgado  2 , Ana Peixoto  4   5 , Ana Barbosa  4   5 , Catarina Santos  4   5 , Nuno Mendes  6 , Paula Lopes  3   7 , Paula Monteiro  3   7 , Ricardo Coelho  8 , Francis Jacob  8 , Viola Heinzelmann-Schwarz  8 , Sara Ricardo  9   10   11 , Manuel R Teixeira  4   5   12 , Carla Bartosch  3   7   12 , Joana Paredes  13   14
Affiliations

P-cadherin overexpression is associated with early transformation of the Fallopian tube epithelium and aggressiveness of tubo-ovarian high-grade serous carcinoma

Rita Canário et al. Virchows Arch. .

Abstract

Tubo-ovarian high-grade serous carcinoma (HGSC) with proficient homologous recombination (HR) DNA repair (HRP) accounts for approximately 50% of cases and is associated with platinum-resistance and poor prognosis. We hypothesize that the acquisition of hybrid phenotypes displaying both epithelial and mesenchymal (E/M) features may be involved in the malignant transformation and tumour dissemination in this subgroup. Therefore, we analysed, by digital pathology, the expression and prognostic significance of 3 classic cadherins (E-cadherin, epithelial marker; N-cadherin, mesenchymal marker; and P-cadherin, candidate marker of hybrid E/M) in 577 formalin-fixed paraffin-embedded human samples representing the putative stepwise serous carcinogenesis in the Fallopian tube epithelium (FTE). We observed a non-canonical N-to-P-cadherin switch along the carcinogenic progression, with a statistically significant overexpression of P-cadherin in pre-malignant and malignant samples, compared to the control FTE. Interestingly, this overexpression was most pronounced in precursor lesions and HGSC cells from malignant ascites. Tumours with high P-cadherin expression were significantly associated with worse overall survival, especially in the subgroup without BRCA1/2 mutations. Transient P-cadherin knock-down resulted in in vitro significant reduction of functional hybrid E/M hallmarks, namely decreased anoikis resistance, reduced collective migration and invasion in a representative platinum-resistant HRP cell line. Taken together, our results suggest that P-cadherin overexpression is an early event in the serous carcinogenesis and may be involved in hybrid E/M activation in HRP-HGSC, further supporting this adhesion molecule as a promising biomarker for this poor prognostic subgroup.

Keywords: CDH3; Epithelial-to-mesenchymal plasticity (EMP); High-grade serous carcinoma; Homologous recombination; P-cadherin.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests.

References

    1. Webb PM, Jordan SJ (2024) Global epidemiology of epithelial ovarian cancer. Nat Rev Clin Oncol 21:389–400. https://doi.org/10.1038/s41571-024-00881-3 - DOI - PubMed
    1. Bowtell DD, Böhm S, Ahmed AA, Aspuria P-J, Bast RC Jr, Beral V et al (2015) Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer. Nat Rev Cancer 15:668–679. https://doi.org/10.1038/nrc4019 - DOI - PubMed - PMC
    1. Bell D, Berchuck A, Birrer M, Chien J, Cramer DW, Dao F et al (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474:609–615. https://doi.org/10.1038/nature10166 - DOI
    1. Stiegeler N, Garsed DW, Au-Yeung G, Bowtell DDL, Heinzelmann-Schwarz V, Zwimpfer TA (2024) Homologous recombination proficient subtypes of high-grade serous ovarian cancer: treatment options for a poor prognosis group. Front Oncol 14:1387281. https://doi.org/10.3389/fonc.2024.1387281 - DOI - PubMed - PMC
    1. Jolly, M.K., J.A. Somarelli, M. Sheth, A. Biddle, S.C. Tripathi, A.J. Armstrong et al (2019) Hybrid epithelial/mesenchymal phenotypes promote metastasis and therapy resistance across carcinomas.

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