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Translational research/biomarkers
2022-RA-1251-ESGO P-cadherin: a promising prognostic biomarker for homologous repair proficient high grade serous ovarian carcinoma
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  1. Rita Canario1,2,3,4,
  2. Inês Morgado2,5,
  3. Ana Sofia Ribeiro2,
  4. Nuno Mendes6,
  5. Paula Lopes7,
  6. Manuel R Teixeira1,4,
  7. Carla Bartosch1,3,7 and
  8. Joana Paredes2,8
  1. 1Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
  2. 2Cancer Metastasis Lab, Instituto de Investigação e Inovação em Saúde Universidade do Porto, Porto, Portugal
  3. 3Cancer Biology and Epigenetics Group, Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto, Portugal
  4. 4Oncogenetics Group, Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto, Portugal
  5. 5Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal
  6. 6Histology and Electron Microscopy, Instituto de Investigação e Inovação em Saúde Universidade do Porto, Porto, Portugal
  7. 7Pathology Department, Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto, Portugal
  8. 8Faculdade de Medicina, Universidade do Porto, Porto, Portugal

Abstract

Introduction/Background Homologous repair (HR) proficient tumours constitute 2/3 of high grade serous ovarian carcinoma (HGSOC), being associated with worse prognosis. Therefore, the identification of clinically relevant biomarkers is an urgent unmet clinical need. Once classic cadherins are transmembrane glycoproteins involved in cell-cell adhesion that are frequently deregulated in cancer, we aimed to: 1) characterize the expression pattern of E-cadherin (CDH1), N-cadherin (CDH2) and P-cadherin (CDH3); 2) evaluate their prognostic impact in terms of overall survival (OS), according to HR status.

Methodology Retrospective study using a convenience sample of archive human tissue (Fallopian tube epithelium (FTE), serous precursor lesions and chemo-naïf HGSOC) from a Portuguese cancer centre. In vitro and in silico validation performed using HGSOC cell lines (BG1 and OVCAR4 cell lines) and CCLE database, respectively. Protein expression evaluated using immunohistochemistry (H-scoring system) and western blot. Comparisons between groups were made using T-test and X2, where appropriate. Survival analyses were estimated using Kaplan-Meier analysis and Log-rank test.

Results We included 321 samples (130 FTE, 53 precursor lesions and 138 HGSOC; 41.2% BRCA1/2 or RAD51D mutated) from 221 patients. All HGSOC co-expressed the 3 cadherins (28% with high co-expression scores). Expression pattern did not differ according to HR status. P-cadherin was significantly upregulated both in precursor lesions and HGSOC, when compared with FTE. CDH3 expression was positively correlated with CDH1, EpCAM and GRHL2 and inversely correlated with VIM, both in silico and in vitro. HGSOC with high cadherin co-expression and high P-cadherin expression were significantly associated with shorter OS in the HR proficient subgroup.

Conclusion Our results suggest that P-cadherin upregulation may be an early event in the serous carcinogenesis and a poor prognosis biomarker in HR proficient HGSOC. Functional assays are currently ongoing to unravel the biological mechanisms underlying P-cadherin role in this subgroup.

https://doi.org/10.1136/ijgc-2022-ESGO.889

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